首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献，搜索用时 46 毫秒
1.
AIM: To study the distribution of 936C/T polymorphism in 3’- untranslated region of vascular endothelial growth factor (VEGF) gene in Chinese Han population and to analyze the relationship between the polymorphism and diabetic retinopathy (DR). METHODS: Two hundred and fifty-four patients with type 2 diabetes mellitus recruited in this study were divided into NPDR group (non-proliferative diabetic retinopathy), PDR group (proliferative diabetic retinopathy) and DM (diabetes without retinopathy) group. The normal control group consisted of 120 subjects. Genotypes were identified by PCR-RFLP among all the subjects, while other clinical parameters were measured. Serum levels of VEGF were tested by the method of ELISA. RESULTS: The frequencies of both genotype CC and allele C were significantly higher in NPDR group and PDR group than those in NC group (2=9.934, 2=4.899, P<0.05 and 2=10.895, 2=5.714, P<0.05) and DM group (2=7.490, 2=4.448, P<0.05 and 2=8.333, 2=5.227, P<0.05). However, the frequencies of genotype (TT+CT) and allele T were significantly lower in NPDR group and PDR group than those in NC group (2=9.934, 2=10.895, P<0.01 and 2=4.899, 2=5.714, P<0.05) and DM group (2=7.490, 2=8.333, P<0.01 and 2=4.448, 2=5.227, P<0.05). Multivariate logistic regression analysis showed that the levels of glycohemoglobin(HbA1c), total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C) and plasma VEGF presented a positive correlation with DR, respectively, and the 936C/T mutation of VEGF exhibited a negative correlation with DR (β=-1.027, OR=0.343, P<0.01, CI: 0.157-0.723). CONCLUSION: Allele 936C of VEGF may be a genetic marker susceptible to DR, while allele 936T may be a protective genetic marker of DR. The 936C/T mutation of VEGF may be a protective factor against DR.  相似文献   

2.
AIM:To investigate the roles of pigment epithelium-derived factor (PEDF), phosphorylated NF-κB p65 and TNF-α in peripheral blood mononuclear cells (PBMCs) in diabetic retinopathy (DR) patients. METHODS:Fifty-two healthy persons were enrolled in the study as normal control group (NC group). Type 2 diabetic patients served as DM group (n=108), which were sub-divided into non-diabetic retinopathy group (NDR group, n=52) and diabetic retinopathy group (DR group, n=56) by angiography. The PBMCs were isolated by the technique of density-gradient centrifugation. The protein levels of PEDF, phosphorylated NF-κB p65 and TNF-α in the PBMCs were determined by Western blotting. The levels of plasma PEDF and TNF-α were detected by ELISA. The content of serum uric acid (SUA) and white blood cell count were measured. RESULTS:The levels of PEDF, TNF-α and phosphorylated NF-κB p65 in the PBMCs were statistically higher in NDR group and DR group than those in control group. The level of TNF-α increased significantly in DR group as compared with NDR group. The levels of PEDF and phosphorylated NF-κB p65 were slightly but not significantly higher in DR group than those in NDR group. The plasma levels of PEDF and TNF-α were evidently elevated in NDR group and DR group compared with NC group, and those were obviously higher in DR group than those in NDR group. In the diabetic patients, the plasma level of PEDF was positively correlated with the levels of TNF-α (r=3.39, P<0.05) and SUA (r=0.25, P<0.05). CONCLUSION:The expression of PEDF in PBMCs is markedly increased, accompanied with the elevation of phosphorylated NF-κB p65 and TNF-α in type 2 diabetic patients especially with DR, suggesting that PEDF is possibly involved in the development of DR by inflammatory mechanism.  相似文献   

3.
AIM: To evaluate the relationship between endothelin-1 (ET-1)/nitric oxide (NO) and hearing impairment in type 2 diabetes mellitus (DM).METHODS: Eighty-eight type 2 diabetic patients with no signs of microangiopathy (retinopathy and nephropathy) or peripheral neuropathy, and 53 healthy subjects in the same period were enrolled in this study. Auditory function was evaluated using pure tone audiometry. Totally,type 2 DM group (n=88) and normal control group (NC, n=53) were divided into subgroups based on the presence and absence of hearing impairment. The concentration of plasma ET-1 was detected by radioimmunoassay. The concentration of serum NO was measured by the method of nitric acid reductase.RESULTS: Significantly increased plasma ET-1 and decreased serum NO were observed in diabetic patients with hearing impairment compared with those in diabetic patients without hearing impairment. The results of multivariate logistic regression analysis showed that hearing impairment in type 2 DM group was significantly associated with elevated level of HbA1c (OR＝4.525, P<0.05), LDL-C (OR=2.381,P<0.05) and plasma ET-1 (OR＝6.207,P<0.01). Besides, elevated serum level of NO (OR＝0.862, P<0.05) was associated with lower risk of hearing impairment in diabetics.CONCLUSION: Hearing impairment may happen earlier than other complications in diabetic patients. In addition to hyperglycemia and hyperlipemia, high level of ET-1 and low levels of NO might contribute to hearing impairment in diabetic patients.  相似文献   

4.
ZHOU Li  LIAN Hui  WANG Zhi-yong 《园艺学报》2018,34(9):1565-1570
AIM:To explore the effects of carnosine (CAR) on cardiac dysfunction in type 1 diabetic mellitus rats and the underlying mechanism. METHODS:The SD rats were randomly divided into 4 groups:control (C) group, control+carnosine (C+CAR) group, diabetes mellitus (DM) group and diabetes mellitus+carnosine (DM+CAR) group (n=10). The rats were sacrificed after 12 weeks. The cardiac function was assessed by ventricular cannulation. The activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA) were assessed by ELISA. The mRNA levels of tumor necrosis factor α(TNF-α), interleukin-1β(IL-1β) and IL-6 were measured by real-time PCR. The distribution of connexin 43 (Cx43) was examined by immunofluorescence. The protein levels of Cx43 and protein kinase C (PKC) were determined by Western blot. RESULTS:Compared with the C group, the left ventricular end diastolic pressure (LVEDP) was increased whereas the left ventricular pressure maximum rise/fall velocity (±dp/dtmax) was decreased in the DM group (P<0.01). The activity of SOD decreased while the MDA increased in the left ventricular tissues (P<0.01). The mRNA levels of TNF-α, IL-1β and IL-6 were increased (P<0.01). The Cx43 distribution was irregular. The protein levels of phosphorylated Cx43 and PKCε were elevated (P<0.01). Compared with the DM group, the cardiac function of LVEDP and ±dp/dtmax in DM+CAR group was ameliorated (P<0.01), with increased SOD activity and decreased MDA content (P<0.05). The mRNA levels of TNF-α, IL-1β and IL-6 were reduced (P<0.01). The Cx43 distribution was improved and the protein levels of phosphorylated Cx43 and PKCε were decreased (P<0.01). CONCLUSION:CAR treatment can improve the cardiac function by its anti-oxidative and anti-inflammation effects and suppression of Cx43 abnormalities through PKCε in DM rats.  相似文献   

5.
AIM：To investigate the effects of Xijiao Dihuang and Yinqiao San decoction (XDY) on the expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in mouse lung tissues and rat pulmonary microvascular endothelial cells (RPMVECs) infected with influenza virus, and to explore its mechanism for treatment of viral pneumonia. METHODS：Fifty-four male BALB/c mice were randomly divided into normal group, model group and XDY group (n=18 in each group). The viral pneumonia model was established by intranasally dripping influenza A (H1N1) virus into the mice. The mice in XDY group were treated with XDY 1 h after dripping the virus. The expression of ICAM-1 and VCAM-1 in lung tissues was examined by immunohistochemical staining 2, 4 and 6 d after infection. On the other hand, RPMVECs were obtained from male Wistar rats and primarily cultured. The cells were randomly divided into control group, virus group, virus+XDY group, tumor necrosis factor α (TNF-α) group and TNF-α+XDY group. The mRNA and protein expression of ICAM-1 and VCAM-1 was evaluated by real-time PCR and flow cytometry 24 h after infection. RESULTS：Virus exposure increased ICAM-1 and VCAM-1 expression in mouse lung tissues (P<0.01), and XDY treatment attenuated this effect (P<0.01). Virus and TNF-α both led to the increases in mRNA and protein expression of ICAM-1 and VCAM-1 in RPMVECs (P<0.01), which were also reduced by treatment with XDY (P<0.01). CONCLUSION：Treatment with XDY decreases virus-induced ICAM-1 and VCAM-1 expression, suggesting an important role of XDY in treatment of viral pneumonia.  相似文献   

6.
AIM: To explore the effects of curcumin analogue L6H4 on the myocardial tissue of type 2 diabetic rats and its mechanism. METHODS: Male Sprague-Dawley rats were randomly divided into normal control (NC) group, high-fat (HF) group, high-fat treatment (FT) group, diabetes mellitus (DM) group and diabetes treatment (DT) group.The rats in the latter 4 groups were fed high-fat diet for 4 weeks, then the rats in DM groups and DT groups were intraperitoneally injected with streptozotocin (STZ) to induce type 2 diabetes, while the rats in FT group and DT group were given L6H4. The blood glucose and lipid levels were detected by biochemical method, and serum adiponectin (APN) levels were detected by ELISA. The serum insulin levels were measured by radioimmunoassay and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated. The morphological changes of myocardium were observed by Masson staining and electron microscopy. The protein expression of adiponectin receptor 1 (AdipoR1) and transforming growth factor β1(TGF-β1) in myocardial tissue were determined by immunohistochemistry. The protein expression of adipoR1 was also detected by Western blot for verification. RESULTS: Compared with NC group, the blood glucose, lipids, insulin, HOMA-IR and TGF-β1 were increased in HF and DM group, but they were decreased after treated with L6H4. Compared with NC group, the concentration of serum APN were decreased and the expression of AdipoR1 in the myocardium were weakened in HF group and DM group, and they increased after treated with L6H4. The myocardial fibrosis was obvious in HF group and DM group, the mitochondria in cardiomyocytes expanded, and the cristae disordered, partial disappeared. These lesions were significantly reduced after L6H4 treatment. CONCLUSION: L6H4 exerts a protective effect on the heart in type 2 diabetic rats. The increased concentration of serum APN, the enhanced expression of AdipoR1, and the expression of TGF-β1 inhibited by APN may be involved in the mechanism of protection.  相似文献   

7.
AIM: To observe the effect of Tangshenfang (TS) on the liver protection and the levels of silent information regulator 1 (SIRT1) and peroxisom proliferator-activated receptor γ coactivator-1α (PGC-1α) in the liver tissue. METHODS: The rat model of diabetes mellitus (DM) was established by intravenous injection of streptozotocin (STZ;30 mg/kg) after having the high fat/high glucose diets for 1 month. The diabetic rats were randomly divided into DM group, DM with high-dose TS (TSHi) group, medium-dose TS (TSMed) group and low-dose TS (TSLow)group. The normal rats were served as control group. There were 8 rats in each group. After treatment with TS for 12 weeks, the serum biochemical indices including fasting blood glucose (FBG), triglyceride (TG), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested. Fasting insulin (FINS) was also detected by radioimmunoassay, and homeostatic model assessment for insulin resistance (HOMA-IR) was calculated. The serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) were measured by ELISA. The activity of SOD and content of MDA in the liver tissues were measured by the methods of hydroxylamine and thiobarbituric acid. The liver pathological changes were observed under light microscope with HE and Masson staining. The protein expression of SIRT1and PGC-1α in the liver tissues was determined by Western blot. RESULTS: In DM group, serum FBG, TG, ALT, AST, FINS, HOMA-IR, TNF-α and IL-1 were obviously increased compared with the control group (P<0.01). The fatty changes, local necrosis, inflammation and fibrosis in the liver tissues were observed. The content of MDA in liver increased, while the activity of SOD decreased markedly. The protein expression of SIRT1 and PGC-1α was decreased (P<0.05). In TS treatment groups, all these changes in DM rats were markedly reversed by TS, and the protein expression of SIRT1 and PGC-1α in the liver tissues was markedly increased. CONCLUSION: TS may protect the rats from diabetic liver injury by increasing the expression of SIRT1 and PGC-1α, and thereby improving insulin resistance and oxidative stress.  相似文献   

8.
AIM: To investigate the protective effect of curcumin analogue L6H4 on diaphragm of type 2 diabetic rats.METHODS: SPF male Sprague-Dawley rats (n=40) were randomly divided into 5 groups: normal control (NC) group, high fat (HF) group, high fat+L6H4 treatment (FT) group, diabetes mellitus (DM) group and DM+L6H4 treatment (DT) group. The rats in the later 4 groups were fed with high-fat diet. After 4 weeks of high-fat diet fee-ding, the rats in DM and DT groups were intraperitoneally injected with streptozotocin to induce type 2 diabetes melliutus. The rats in FT and DT groups were given L6H4 by gavage for 8 weeks. Blood glucose and blood lipid levels were detected biochemically. Fasting serum insulin (FINS) level was measured by radioimmunoassay and insulin resistance index (HOMA-IR) was calculated. Serum adiponectin (APN) level was measured by ELISA. The morphological changes of the diaphragm were observed under light and transmission electron microscopes. Lipid deposition and the activity of succinate dehydrogenase (SDH) and NADH-tetrazolium reductase (NADH-TR) were observed by enzyme histochemical staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD) in the diaphragm were measured by thiobarbituric acid method and hydroxylamine method, respectively. The protein expression of adiponectin receptor 1 (AdipoR1) in the diaphragm was determined by immunohistochemistry and Western blot. RESULTS: The levels of blood lipids, blood glucose, FINS and HOMA-IR in HF and DM groups were higher than those in NC group, but decreased after L6H4 treatment. The serum APN level in HF and DM groups was lower than that in NC group, but increased after treatment with L6H4. The muscle fibers of the diaphragm were shrunk, fat particles accumulated in the muscle fibers, and the mitochondria were slightly swollen in HF and DM groups. The diaphragmatic fibrosis was obvious in DM group. These lesions were relieved after L6H4 treatment. Compared with NC group, the level of MDA and the activity of SDH and NADH-TR in the diaphragm were increased in HF and DM groups, but decreased after treatment with L6H4. The activity of SOD and the expression of AdipoR1 in the diaphragm were lower than those in NC group, but increased after L6H4 treatment.CONCLUSION: The curcumin analogue L6H4 exerts a protective effect on diaphragm in type 2 diabetic rats. The strengthened protein expression of AdipoR1, the increased serum level of APN, and anti-lipid peroxidation may be involved in the process.  相似文献   

9.
AIM: To investigate the ameliorative effect of salvianolic acid B on vasodilatory function in diabetic rats and the possible mechanisms. METHODS: SD rats (n=40) were fed on high-sugar and high-fat diet for 4 weeks, followed by a single intraperitoneal injection of streptozotocin (40 mg/kg). The rats with random blood glucose level over 16.7 mmol/L were considered diabetic and randomly allocated to 3 groups, namely model group, low dose (80 mg·kg-1·d-1) of salvianolic acid B group and high dose (160 mg·kg-1·d-1) of salvianolic acid B group. The rats in salvianolic acid B groups were intragastrically administered with corresponding doses of salvianolic acid B for 6 weeks. Vasodilatory function was measured as endothelium-dependent and-independent vasodilation of the aortic rings. The primary histopathological changes of aorta were observed by HE staining. Serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) were measured by ELISA. The levels of total antioxidant capacity, malondialdehyde (MDA) and nitric oxide (NO) in aortic tissues were evaluated by colorimetric assays. The protein levels of intercellular adhesion molecule-1 (ICAM-1) and monocyte chemotactic protein-1 (MCP-1), and the activation of nuclear factor-κB (NF-κB) were determined by Western blot. RESULTS: Treatment with salvianolic acid B evidently ameliorated endothelium-dependent diastolic function and pathological changes of aorta in diabetic rats (P<0.05 or P<0.01). Supplementation with salvianolic acid B resulted in significant increases in NO content and total antioxidant capacity in aortic tissues, accompanied by marked decreases in the level of MDA in aorta tissues and the serum levels of IL-6, TNF-α and CRP (P<0.05 or P<0.01). Salvianolic acid B markedly down-regulated NF-κB p65 nuclear translocation and protein expression of ICAM-1 and MCP-1 in aorta tissues (P<0.05 or P<0.01). CONCLUSION: Salvianolic acid B effectively ameliorates endothelium-dependent diastolic function of aorta in diabetic rats, which might be attributed to suppression of NF-κB activation and subsequent expression of inflammatory cytokines. The beneficial effect of salvianolic acid B on vascular endothelium might be derived from its antioxidant capacity.  相似文献   

10.
AIM: To investigate the gene polymorphism-308 of tumor necrosis factor alpha (TNF-α) in the relation with the susceptibility to periodontitis combined with type 2 diabetes mellitus (DM) and its severity.METHODS: Human DNA samples were obtained from 240 DM patients with periodontitis (periodontitis group, n=120) and without periodontitis (control group, n=120). All patients were genotyped by PCR-RFLP analysis. The frequencies of genotypes and alleles were analyzed. Sulcus bleeding index (SBI) and probing depth (PD) in all patients were measured. The polymorphism-308 of TNF-α gene in the relation with the susceptibility to periodontitis combined with DM and its severity was analyzed.RESULTS: No significant difference in the frequency of genotype and allele was found between DM patients with mild periodontitis and DM patients without periodontitis (P>0.05). However, the frequencies of these genotypes and alleles in DM patients with moderate and severe periodontitis were significantly higher than those in DM patients without periodontitis (P<0.01). The findings showed that the level of TNF-α was associated with SBI and PD (P<0.01).CONCLUSION: TNF-α -308 G/A polymorphism is not associated with DM patients with mild periodontitis, whereas it may have a role in pathogenesis and prognosis of moderate and severe periodontitis combined with DM through TNF-α level.  相似文献   

11.
AIM: To investigate the serum levels of apelin and chemerin in female obese children and their correlation with insulin resistance (IR).METHODS: Thirty-five female children participated in the study, 20 of which were obese and 15 were non-obese controls ,without statistical difference in age between the 2 groups. Serum levels of apelin and chemerin were measured by ELISA method. The concentrations of triglyceride (TG), cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting glucose and fasting insulin (FINS) were measured. Body mass index standard deviation score (BMI-SDS) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated for all participants. RESULTS: A significant difference of BMI between obese group and control group (24.02±3.90 vs 16.46±1.93, P<0.01) was observed. Serum levels of TG, LDL-C, FINS, and HOMA-IR were significantly higher in obese group than those in control group (allP<0.05). Serum levels of apelin and chemerin were also significantly higher in obese children than those in the controls . Serum level of apelin was positively correlated with BMI-SDS (r=0.356, P<0.05), TG (r=0.548, P<0.01), FINS (r=0.541, P<0.01) and HOMA-IR (r=0.551, P<0.01) in all individuals. The negative correlation between serum chemerin level and age (r=-0.362, P< 0.05), and positive correlations between serum chemerin level and BMI-SDS (r= 0.315, P<0.01), TG (r= 0.28, P<0.05), FINS (r= 0.38, P<0.01) and HOMA-IR (r= 0.41, P< 0.01) were detected.CONCLUSION: Increased serum apelin and chemerin levels are correlated with insulin resistance, indicating their roles in the pathogenesis of children obese.  相似文献   

12.
AIM: To observe the effects of Egr-1 gene transfection on the expression of tumor necrosis factor-α(TNF-α) and intercellular adhesion molecule-1(ICAM-1), and to investigate the role of Egr-1 in the pathogenesis of diabetic nephropathy.METHODS: The diabetic mouse model was established. Ten mice were randomly selected as the diabetic group. The remaining 40 mice were injected with empty plasmid, Egr-1 expression plasmid or Egr-1 siRNA plasmid via the tail vein once a week. The normal control group was also set up. The animals were sacrificed at the end of the 4th week. The renal tissues were harvested. The expressions of Egr-1, TNF-α and ICAM-1 were detected by immunohistochemistry and Western blot. The pathological changes were observed under electron microscope.RESULTS: In diabetic mouse kidney, the expression of Egr-1, TNF-α and ICAM-1 was increased, and irregular thickening of glomerular basement membrane, mesangial expansion and fusion of foot were observed. The change trend was more significant in Egr-1 gene transfection group, and these changes in siRNA plasmid transfection group were obviously reduced compared with diabetes group.CONCLUSION: Egr-1 up-regulates the expression of TNF-α and ICAM-1, and induces mesangial cell proliferation and mesangial extracellular matrix accumulation, which is probably one of the mechanisms of accelerating glomerulosclerosis.  相似文献   

13.
AIM: To explore the serum levels of visfatin (VF) and tumor necrosis factor-alpha (TNF-α) in the patients with pre-eclampsia (PE) and their correlation with insulin resistance (IR). METHODS: The severe PE patients (n=30), mild PE patients (n=30) and normal pregnant women (n=40) were selected according to the classification standard of PE. The serum levels of VF and TNF-α were measured by ELISA. Fasting plasma glucose (FPG) and fasting insulin (FIns) were detected by glucose oxidase method and radioimmunoassay, respectively. Triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured by an automatic biochemical analyzer. According to calculating the mean arterial pressure (MAP), body mass index (BMI) and homeostatic model assessment for insulin resistance index (HOMA-IR), the correlation between IR and the levels of serum VF as well as TNF-α were analyzed.RESULTS: The levels of VF and TNF-α in severe PE group and mild PE group were significantly lower than those in normal pregnancy group (P<0.05). In addition, the levels of VF and TNF-α in severe PE group were lower than those in mild PE group (P<0.05). Linear correlation analysis showed that serum VF was positively correlated with TNF-α and HDL-C (P<0.05), and negatively with MAP and FIns (P<0.05). The serum TNF-α was positively correlated with HDL-C (P<0.05), and negatively with BMI, TG, MAP and FIns (P<0.05). Multiple stepwise regression analysis showed that FBG, FIns and HOMA-IR were relative independent factors of serum VF and TNF-α (P<0.05).CONCLUSION: Serum levels of VF and TNF-α are closely related to IR.  相似文献   

14.
AIM: To explore the effect of mycophenolate mofetil (MMF) on expression of osteopotin (OPN) and macrophage colony stimulating factor (M-CSF) in diabetic rats with renal tubulo-interstitial injury. METHODS: Diabetes was induced in uninephrectomized male Wistar rats by peritoneal injection of streptozotocin (65 mg/kg). The rats were randomly divided into three groups: control group (NC), diabetic group (DM) and MMF treated group ［DM+MMF, treatment of MMF (15 mg·kg-1·d-1) by gavage from the next day of the induction for 8 weeks］. Serum biochemistry, 24 h urinary protein and the ratio of left kidney weight/body weight were determined after 8 weeks. The renal tubulo-interstitial morphological change was observed, immunohistochemical method was used to analyze the expression of OPN, M-CSF and CD68. The mRNA of OPN in renal tissue was amplified by quantitative real-time PCR. RESULTS: Compared with control group, serum glucose level, 24 h urinary protein and the ratio of left kidney weight/body weight were significantly increased (P<0.01), and the relative area of interstitial fibrosis was also significantly enlarged in DM group (P<0.01).Compared with NC group, the expressions of OPN, M-CSF, CD68 protein and OPN mRNA were significantly upregulated in DM group (P<0.01). After intervention with MMF, the upregulations of the above-mentioned parameters, except blood glucose and serum creatinine, were all significantly inhibited (P<0.05 or P<0.01). CONCLUSION: The expressions of OPN, M-CSF and CD68 in renal tubulointerstitial decrease in diabetic rats treated with MMF. MMF also inhibits the level of OPN mRNA, reduces proteinuria and prevents renal injury. MMF plays an apparently protective role in renal tubulointerstitial injury, probably associated with inhibiting chemokine and proliferation on macrophages.  相似文献   

15.
AIM：To explore the dynamic change of focal adhesion kinase (FAK) in renal tissues of rats with type 2 diabetes mellitus (T2DM), and to investigate its role in the pathogenesis of diabetic nephropathy (DN). METHODS：The rat model of T2DM was established and the diabetic rats were randomly divided into 8-week DM (DM8), 12-week DM (DM12) and 16-week DM (DM16) groups. Meanwhile, normal control (NC) and high-fat high-sucrose control (HC) groups were also established. The protein expression of FAK, transforming growth factor β1 (TGF-β1), extracellular signal-regulated kinase 1/2 (ERK1/2), p-ERK1/2 and fibronectin (FN) was detected by immunohistochemical staining. The protein levels of FAK and p-FAK (Tyr397) were detected by Western blotting. The mRNA level of FAK in the renal cortex was examined by RT-PCR. RESULTS：The expression of FAK protein in renal tubular epithelial cells in DM12 and DM16 groups was significantly higher than that in NC, HC and DM8 groups (P<0.05). Moreover, TGF-β1, p-ERK1/2 and FN protein expression in DM groups was significantly increased compared with NC and HC groups (P<0.05). The levels of FAK and p-FAK (Tyr397) in the renal cortex in DM12 and DM16 groups were significantly up-regulated compared with NC, HC and DM8 groups (P<0.05), and the expression trend of p-FAK in different groups was in accordance with that of total FAK. The FAK protein expression was positively correlated with the expression of TGF-β1, p-ERK1/2 and FN proteins (P<0.01). Compared with NC, HC and DM8 groups, the expression of FAK mRNA increased remarkably in DM12 and DM16 groups (P<0.05). CONCLUSION: There is a possibility that FAK is activated as a downstream effector of TGF-β1 in T2DM, which enhances the expression of FN protein through activating ERK1/2, and therefore plays an important role in the pathogenesis of type 2 diabetic nephropathy.  相似文献   

16.
AIM: To study the production of intercellular adhesion molecule-1(ICAM-1), E-selectin and P-selectin in serum, lung tissues and bronchoalveolar lavage fluid(BALF)of acute lung injury(ALI) model and to observe the effects of ambroxol combined with low-dose heparin on the changes of the 3 factors above.METHODS: Twenty-four healthy rabbits were randomly divided into 3 groups: normal saline control group (NC), oleic acid injury group (OA), ambroxol+ heparin treatment group (AH). The rabbit ALI model was induced by oleic acid injection through auricular vein. Partial pressure of O2 in artery(PaO2) was analyzed.The concentrations of ICAM-1 and E-selectin were detected by ELISA.The apoptosis index(AI) was measured by TUNEL method.The expression of P-selectin was determined by immunohistochemical method.The ultrastructural changes of the lung tissues were observed under electron microscope, and the lung wet/dry ratio(W/D) was calculated.RESULTS: PaO2 in AH group and OA group was significantly lower (P<0.01) than that in NC group, and PaO2 in AH group was significantly higher than that in OA group (P<0.01). The concentrations of ICAM-1 and E-selectin in serum, lung tissues and BALF, and AI and W/D in lung tissues in AH group were higher (P<0.05 or P<0.01) than those in NC group, and was lower than those in OA group (P<0.05 or P<0.01). In NC group, no significant change of the above parameters at all time points was observed (P>0.05). In OA group, PaO2 was significantly decreased (P<0.01) with the pathological process developed, and the concentrations of ICAM-1 and E-selectin were significantly increased. In AH group, PaO2 was decreased (P<0.05),and the concentrations of ICAM-1 and E-selectin were increased with the process of ALI developed. The P-selectin expression in lung tissues of OA group was distributed mainly in inflammatory cells, capillary endothelial cells and plasma. From low to high levels, the order was NC group < AH group < OA group in the expression of P-selectin. The most obvious apoptosis was observed in OA group. No apoptosis or occasional positive cells were found in NC group. The apoptotic rate in AH group was significantly reduced compared with that in OA group.CONCLUSION: In ALI induced by OA, ICAM-1, E-selectin and P-selectin are significantly increased and are involved in the occurrence and development of ALI. Ambroxol combined with low-dose heparin reduces the levels of ICAM-1, E-selectin and P-selectin, the pulmonary edema and the lung injury, improves pulmonary functions, and plays an important role in the prevention and treatment of acute lung injury.  相似文献   

17.
AIM: To investigate the different effects of adiponectin (APN) and adiponectin receptor 1 (Ad-R1) on myocardial ischemia-reperfusion (IR) injury and ischemic preconditioning (IPC) in different course of diabetic rats in vitro. METHODS: The rat models of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) were successfully established using streptozotocin and high-fat diet plus streptozotocin, respectively. These rats were divided into 2 groups:4 weeks and 8 weeks. The model of isolated cardiac perfusion was established by Langendorff method. Each group was further divided into control (Con) group, IR group and IPC group. The activity of lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary effluent was detected. The serum and myocardial levels of APN were determined by ELISA. The expression of Ad-R1 in the myocardial tissues was detected by Western blot. The area of myocardial infarction was detected, and the ultrastructure of ventricular papillary muscle was observed by transmission electron microscopy. RESULTS: Compared with the corresponding IR group, the activity of LDH and CK in the IPC group at 4 weeks was significantly decreased (P<0.01), and the area of myocardial infarction was significantly reduced. However, no significant difference of each index in DM groups at 8 weeks was observed. Serum APN level was decreased in diabetic rats, especially in T2DM rats (P<0.05). The levels of APN and Ad-R1 in myocardium of normal rats had no difference among Con, IR and IPC groups. The level of APN in myocardium of T1DM rats had no difference in all subgroups, while the expression of Ad-R1 in myocardial tissue of IR group was significantly increased as compared with Con group (P<0.01) and IPC group (P<0.01) both at 4 and 8 weeks. In T2DM rats, the levels of APN in myocardium both at 4 and 8 weeks were decreased in IR group compared with Con group (P<0.05). The level of APN in IR group at 4 weeks was significantly decreased compared with IPC group, but had no significant difference at 8 weeks. The expression of Ad-R1 in myocardial tissue of IR group was significantly increased compared with Con group (P<0.05) both at 4 and 8 weeks. The level of Ad-R1 in IR group at 4 weeks was significantly increased compared with IPC group (P<0.05), but had no significant difference at 8 weeks. CONCLUSION: The protective effect of IPC exists in diabetic rats at 4 weeks, whereas it disappears at 8 weeks. APN and Ad-R1 in myocardium were probably involved in the protective effect of IPC on T2DM rats.  相似文献   

18.
AIM：To investigate whether hydrogen sulfide (H2S) protects the hearts against inflammatory responses induced by acute myocardial ischemia in isolated rat hearts. METHODS：Rat acute myocardial ischemia injury was induced by ligation of the left anterior descending coronary artery for 4 h, and the normal perfusate was replaced with NaHS (5 μmol/L, 10 μmol/L and 20 μmol/L) perfusate accordingly in NaHS groups 2 h after ischemia. The changes of cardiac function in the myocardial ischemic injury rats were observed. The mRNA expression of TNF-α, IL-1β, IL-6, IL-10 and ICAM-1 was detected by real-time PCR. The protein level of nuclear factor-κB (NF-κB) in the myocardial tissues was detected by Western blotting. RESULTS：The cardiac function in ischemia group was lower than that in sham group (P<0.01). Compared with ischemia group, perfusion of NaHS resulted in the improvement of the cardiac function (P<0.05 or P<0.01). Compared with sham group, the mRNA expression of TNF-α, IL-1β, IL-6 and ICAM-1 in the cardiac tissues was significantly increased, and the mRNA expression of IL-10 in the cardiac tissues was significantly decreased in ischemia group (P<0.01). Compared with ischemia group, the perfusion of NaHS significantly decreased the mRNA expression of TNF-α, IL-1β, IL-6 and ICAM-1 (P<0.05 or P<0.01). The perfusion of NaHS at concentrations of 10 μmol/L and 20 μmol/L significantly increased the mRNA expression of IL-10 (P<0.01). The protein level of NF-κB in ischemia group was markedly higher than that in sham group (P<0.01). Compared with ischemia group, the perfusion of NaHS at concentrations of 10 μmol/L and 20 μmol/L significantly decreased the expression of NF-κB (P<0.05 or P<0.01). CONCLUSION：H2S protects the hearts against acute ischemia injury through inhibition of NF-κB activation and subsequent down-regulation of NF-κB-dependent inflammatory gene expression.  相似文献   

19.
AIM：To establish the insulin resistance rat model for evaluating the correlation of omentin-1 level and insulin resistance. METHODS：SPF male Wistar rats (n=30) were randomly divided into normal control group (NC, n=15) and high-fat diet group (HF, n=15). The rats in NC group were fed with basic diet. The insulin resistant model was established by feeding the rats with high-fat diet in HF group. After 10 weeks, 5 rats in each group were assessed by the technique of hyperinsulinaemic-euglycaemic clamp. After the insulin resistant model was successfully established, the body weight and fasting blood glucose were detected. The concentration of fasting serum omentin-1 was analyzed by ELISA. Fasting serum insulin was measured by radioimmunoassay. RESULTS：No difference of fasting blood glucose between the 2 groups was observed. The level of fasting serum insulin in HF group was significantly higher than that in NC group (P<0.05). The level of serum omentin-1 in HF group were significantly decreased compared with NC group (P<0.01). Pearson’s correlation analysis showed that negative correlations between serum omentin-1 and fasting serum insulin (r=-0.654,P<0.01), serum omentin-1 and free fatty acid (r=-0.446, P<0.05) was found. CONCLUSION：In rats, serum omentin-1 level began to decrease at insulin resistance stage. As serum omentin-1 level decreased, the basal insulin level increased, indicating that decreased serum omentin-1 level may be an early factor of IR, diabetes and cardiovascular diseases.  相似文献   

20.
AIM: To explore the mechanism of propolis on the inhibition of atherosclerosis and thrombosis in injured human umbilical vascular endothelial cells (HUVECs) induced by tumor necrosis factor alpha (TNF-α)in vitro.METHODS: TNF-α at the concentration of 50 μg/L was used to induce the injury of HUVECs. The injured HUVECs were treated with water extract propolis (WEP) at the concentrations of 50, 100 and 200 mg/L for 6 h, 12 h and 24 h. The expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) was examined by flow cytometry.RESULTS: The expression of ICAM-1 and VCAM-1 was significantly higher in injured HUVECs (P<0.01) than that in the control cells. The expression of ICAM-1 and VCAM-1 was downregulated by WEP treatment in a dose-dependent manner. Between the groups of 100 and 200 mg/L WEP, the difference was significant. In the injured HUVECs treated with 50 mg/L WEP, the inhibitory effect on the expression of ICAM-1 and VCAM-1 was presented in a time-dependent manner. Compared to the single administration, the use of WEP combined with fluvastatin showed better inhibitory effect on the expression of ICAM-1 and VCAM-1 in the injured HUVECs induced by TNF-α (P<0.01).CONCLUSION: WEP may be helpful for the protection of vascular endothelial cells by inhibiting the expression of ICAM-1 and VCAM-1 in a time-and dose-dependent manner. The protective effect of WEP on endothelial cells may be synergic with the inhibitor of HMG-CoA reductase such as fluvastatin sodium.  相似文献   

设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号