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1.
AIM: To observe the change of CX3CL1/fractalkine (FKN) in the rats with monocrotaline-induced pulmonary hypertension, and to study the intervention of puerarin. METHODS: The pulmonary hypertension model was established in vivo by intraperitoneal injection of monocrotaline. Thirty male Sprague-Dawley rats (270-310 g) were randomly divided into 3 groups: control group (C), monocrotaline model group (M)and puerarin treatment group (M+P). The mean pulmonary arterial pressure (mPAP), mean right ventricular pressure (mRVP), mean carotid arterial pressure (mCAP) and the weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) were also detected. The structural changes of pulmonary arterioles were observed under optical microscope. Remodeling of lung blood vessels was determined by measuring the ratio of vessel wall area to total area (WA/TA) and the medium thickness of pulmonary artery (PAMT). The concentration of soluble fractalkine(sFKN) in plasma was measured by ELISA. The expression of FKN in the pulmonary artery wall was measured by immunohistochemistry. The mRNA level of FKN in the lung tissues was detected by RT-PCR.RESULTS: mPAP, mRVP, RV/(LV+S), WA/TA and PAMT in M group were higher than those in C group (P<0.01). RV/(LV+S), WA/TA and PAMT in M+P group were significantly lower than those in M group (P<0.01). No significant difference of mCAP among the 3 groups was observed. The levels of sFKN, FKN mRNA and FKN protein in M group were higher than those in C group (P<0.01), and the above data in M+P group were lower than those in M group(P<0.05). The serum level of sFKN had a positive correlation with PAMT and RV/(LV+S) (r＝0.719, r=0.685,respectively, P<0.01).CONCLUSION: Puerarin down-regulates the expression of FKN and suppresses the development of pulmonary hypertension and pulmonary vessel remodeling.  相似文献   

2.
AIM: To observe the effect of Panax notoginoside (PNS) on the pulmonary artery pressure and the p38 mitogen-activated protein kinase(p38 MAPK) in lung tissues of rats treated with hypoxia. METHODS: Thirty adult male SD rats were randomly divided into 3 groups. The rats in normal control group were exposed to normal conditions, the rats in hypoxia group were exposed to isobaric hypoxia, and the rats in hypoxia+PNS group were treated with PNS under the condition of hypoxia. After 4 weeks of treatment, the mean pulmonary arterial pressure (mPAP) and the mean carotid arterial pressure (mCAP) were measured by cardiac catheterization. The heart was isolated, and the right ventricle (RV), left ventricle plus ventricular septum (LV+S) were weighed to calculate the ratio of RV/(LV+S).The quantity of phospho-p38 MAPK(p-p38 MAPK) in rat pulmonary arterioles was determined by the method of immunohistochemistry and the mRNA content of p38 MAPK was tested by RT-PCR. RESULTS: The mPAP and RV/(LV+S) in hypoxia group were higher than those in normal control group. The expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues were higher than those in normal control group (P<0.05). The mPAP, RV/(LV+S), the expression of p-p38 MAPK in rat pulmonary arterioles and p38 MAPK mRNA in the lung tissues in hypoxia+PNS group were significantly lower than those in hypoxia group (P<0.05).CONCLUSION: PNS possesses the preventive and therapeutic effect on hypoxic pulmonary hypertension by decreasing p-p38 MAPK and down-regulation of p38 MAPK mRNA in the lungs.  相似文献   

3.
AIM: To explore the effects of hydroxylamine on the pulmonary arterial pressure in chronic hypoxic hypercapnic rats. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into 3 groups (8 rats in each group): the normal control group (NC), hypoxic hypercapnia+normal saline group (NS), hypoxic hypercapnia+hydroxylamine group (HA). The animals in NS and HA groups were kept in the O2 (9%-11%) and CO2 (5%-6%) cabin, 8 h a day and 6 days a week for 4 weeks. Before entering the cabin, the rats in HA group were administered with 1 mL hydroxylamine (12.5 mg/kg) by intraperitoneal injection, while the rats in NS group were given intraperitoneal injection of 1 mL saline solution. The mean pulmonary arterial pressure (mPAP) was measured by external jugular vein cannulation. The heart was removed, and the right ventricle (RV) and the left ventricle plus the septum (LV+S) were dissected. The ratio of the wet weight of the RV to that of the LV+S was calculated. The changes of the pulmonary vascular construction were observed under optical microscope. The concentration of H2S in the plasma was measured with a spectrometer. The expression of cystathionine-γ-lyase (CSE) in the pulmonary arterioles and bronchi was measured by immunohistochemistry and RT-PCR. RESULTS: The values of mPAP, RV/(LV+S),vessel wall area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) in NS group and HA group were significantly higher than those in NC group (P<0.05). The level of H2S in the plasma, the content of CSE protein and the expression of CSE mRNA in NC group were significantly lower than those in NS group (P<0.05). The values of mPAP, RV/(LV+S), WA/TA and PAMT in HA group were significantly lower than those in NS group (P<0.05). The level of H2S in the plasma, the content of CSE protein and the expression of CSE mRNA in HA group were significantly higher than those in NS group (P<0.05). CONCLUSION: Hydroxylamine may decrease the pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats by increasing the level of H2S in the plasma, the content of CSE protein and the mRNA expression of CSE, thus improving the pulmonary vascular structural remodeling.  相似文献   

4.
AIM: To study the protective effect of A2a adenosine receptor (A2aAR) on hypoxic pulmonary hypertension in the rats treated with salidroside. METHODS: Sprague-Dawley rats were randomly divided into 6 groups: normal control group, hypoxia group, hypoxia+salidroside (low dose) group, hypoxia+salidroside (median dose) group, hypoxia+salidroside (high dose) group, and hypoxia+CGS-21680 (a selective agonist of A2aAR) group. Pulmonary hypertension in the rats was produced for 4 weeks. Mean pulmonary artery pressure (mPAP), mean carotid arterial pressure (mCAP) and the weight ratio of right ventricle/(left ventricle+septum)［RV/(LV+S)］ were measured. The expression of A2aAR in the pulmonary arterioles was determined by immunohistochemistry and in situ hybridization. The mRNA expression of A2aAR in the lung tissues was detected by real-time RT-PCR. The protein level of A2aAR in the lung tissues was analyzed by Western blotting. RESULTS: The mPAP in hypoxia group was significantly higher than that in normal control group. The mPAP in hypoxia+salidroside (high dose) group and CGS-21680 group was significantly lower than that in hypoxia group. RV/(LV+S) in hypoxia group were significantly higher than that in normal control group. RV/(LV+S) in hypoxia+salidroside (median dose) group, hypoxia+salidroside (high dose) group and CGS-21680 group were lower than that in hypoxia group. The ratio of vessel wall area/vessel total area (WA/TA) in hypoxia group was significantly higher than that in normal control group. WA/TA in hypoxia+salidroside (low dose) group, hypoxia+salidroside (median dose) group, hypoxia+salidroside (high dose) group and CGS21680 group were obviously lower than that in hypoxia group. The expression of A2aAR was significantly higher in hypoxia group than that in normal control group. The expression of A2aAR in hypoxia+salidroside (high dose) group and CGS-21680 group was obviously higher than that in hypoxia group. CONCLUSION: The A2aAR attenuates pulmonary vessel remodeling and pulmonary hypertension induced by hypoxia. Salidroside protects the pulmonary vessel from remodeling and inhibits the development of hypoxia-induced pulmonary hypertension by up-regulation of A2aAR expression.  相似文献   

5.
AIM: To study whether salidroside plays a protective role in hypoxia-induced pulmonary hypertension by suppressing oxidative stress. METHODS: Sprague-Dawley rats were randomly divided into 4 groups:normoxia (N) group, hypoxia for 4 weeks (H4) group, low-dose salidroside (hypoxia for 4 weeks and treatment with salidroside at 16 mg/kg, H4S16) group and high-dose salidroside (hypoxia for 4 weeks and treatment with salidroside at 32 mg/kg, H4S32) group. The mean pulmonary arterial pressure (mPAP), the weight ratio of right ventricle/(left ventricle+septum)[RV/(LV+S)] and vessel wall area/vessel total area (WA/TA) were evaluated. The levels of malondialdehyde (MDA) in the serum and lung tissues were detected by colorimetric method. The levels of 8-iso-prostaglandin F2α (8-iso-PGF2α) in the serum and lung tissues were measured by ELISA. The activity of superoxide dismutase (SOD) in the serum was analyzed by hydroxylamine method. The expression of NAPDH oxidase 4 (NOX4) and SOD1 in the lung tissues was determined by Western blot. RESULTS: Compared with N group, the levels of mPAP, RV/(LV+S) and WA/TA in H4 group were significantly increased, which were apparently attenuated by salidroside injection in a dose-dependent manner. Meanwhile, salidroside administration apparently decreased the levels of MDA and 8-iso-PGF2α in the serum and lung tissues, as well as the expression of NOX4 in the lung tissues. Besides, compared with N group, the activity of SOD in the serum and the expression of SOD1 in the lung tissues in H4 group were significantly decreased, while administration of salidroside increased the activity of SOD in the serum and the expression of SOD1 in the lung tissues in a dose-dependent manner. CONCLUSION: Salidroside protects the pulmonary vessels from remodeling and attenuates hypoxia-induced pulmonary hypertension by inhibiting oxidative stress.  相似文献   

6.
AIM: To study the role of adrenomedullin(AM) in the pathogenesis of hypoxic pulmonary hypertension. METHODS: Rats were exposed to chronic hypoxia for 14 days. After the measurement of the right ventricular systolic pressure (RVSP), the rats were executed. The weight of the right ventricle (RV), the left ventricle(LV) and the ventricular septum(SP) were determined. The ration RV/(LV+SP) was used to express the thickness of RV. In situ hybridization was used for the detection of the expression of AM mRNA in the lung and RV. RESULTS: The RVSP in the hypoxic group was (63.63±3.42) mmHg,which was significantly higher than that in control group [(34.13±3.40) mmHg]. The RV/(LV+SP) in hypoxic group was 0.439±0.039,which was increased obviously when compared with that of control (0.230±0.025). The level of AM mRNA expressed in the RV in the hypoxia group was significantly higher than that in the control group. CONCLUSION: The expression of AM mRNA in RV increased in the hypoxic condition, which suggests that AM may attenuate the inappropriate increase in pulmonary artery pressure.  相似文献   

7.
AIM: To investigate the roles of nitric oxide/L-arginine (NO/L-Arg) pathway and urotensin-Ⅱ (UⅡ) in the development of pulmonary hypertension induced by chronic hypoxia-hypercapnia in rats.METHODS: Forty male Sprague-Dawley rats were randomly divided into four groups (n=10): normal control group (A), hypoxia-hypercapnia+saline group (B), hypoxia-hypercapnia+L-Arg liposome group (C) and hypoxia-hypercapnia+N-nitro-L-arginine methyl ester (L-NAME) group (D).Contents of UⅡ, UⅡ mRNA and receptor of UⅡ (UT) mRNA in pulmonary arterioles were measured with immunohistochemistry analysis and in situ hybridization, respectively.Change of small pulmonary vascular microstructure was also investigated.RESULTS: (1) The mean pulmonary artery pressure (mPAP) and the weight ratio of right ventricle to left ventricle plus septum ［RV/(LV+S)］ in B and D groups were all higher than those in A group (respectively, P<0.05), with C group significantly lower than those in B group (respectively, P<0.01).(2) Light microscopy showed that the ratio of vessel wall area to total area (WA/TA) and the media thickness of pulmonary arterioles (PAMT) in B group were higher than those in A group (P<0.05), with C group significantly lower than those in B group.(3) The contents of UⅡ, UⅡ mRNA and UT mRNA in pulmonary arterioles in B and D groups were all higher than those in A group (respectively, P<0.01), while the expression of UⅡ and UⅡ mRNA in C group were lower than those in B group (P<0.01).CONCLUSION: The pathological process of pulmonary hypertension induced by chronic hypoxia-hypercapnia might be related to upregulation of UⅡ located in pulmonary arterioles, which might be partially inhibited by exogenous NO in rats.  相似文献   

8.
AIM:To study the effects of airway and pulmonary inflammation on pulmonary arterial remodeling in rats with chronic bronchitis (CB) and emphysema.METHODS:Twenty-four male Wistar rats were divided into three groups (n=8): Group A: four-weeks CB and emphysema;Group B: six-weeks CB and emphysema group;Group C: normal control.The rat model of CB and emphysema was established by intratracheal instillation of lipopolysaccharide (LPS) and daily exposure to cigarette smog.The arterial blood gas analysis,pulmonary hemodynamics changes and cell counts in bronchoalveolar lavage fluid (BALF) were measured.The pathomorphological changes of airway inflammation,alveoli destruction and pulmonary arterial remodeling were observed by HE straining and triple straining.RESULTS:(1) The characteristic pathological changes of CB and emphysema were observed in group A and B.Neutrophils were the main cells infiltrated into the walls of airway in group A.Lymphocytes and macrophages were the main cells in group B.(2) Right ventricular systolic pressure (RVSP),mean pulmonary arterial pressure (mPAP),the ratio of the weight of right ventricle/left ventricle and septum (RV/LV+S) in group A and B were significantly higher than those in group C (P<0.05).The amount of muscular artery (MA) in group A and B were significantly higher than that in group C (P<0.05).(3) In group A and B,the levels of MA,RVSP,mPAP and RV/LV+S was correlated positively with the average alveolar area,the total cell counts and differential cell counts of neutrophils,lymphocytes and macrophages in BALF,and the level of infiltration into the walls of airway,respectively (P<0.05).The positive correlation was observed with the percentage of neutrophils,lymphocytes and macrophages between group A and B (P<0.05).The amounts of MA were also correlated positively with RVSP,mPAP and RV/LV+S (P<0.05).CONCLUSIONS:(1) The pulmonary artery hypertension,the right ventricular hypertrophy and the pulmonary arterial remodeling appeared before hypoxia.These may be related with the degree of the pulmonary inflammation.(2) The characteristic of pulmonary arterial remodeling was small artery organization,and correlated positively with the changes of hemodynamics.  相似文献   

9.
LU Bang-chao  ZOU Da-jin 《园艺学报》2011,27(9):1832-1835
AIM: To investigate the effect of p38 MAPK signal pathway on cerulein-treated pancreatic acinar AR42J cells.METHODS: AR42J cells were divided into control group, cerulein group (treated with 10-8 mol/L of cerulein), and SB203580 group (treated with 10 μmol/L of SB203580 and 10-8mol/L of cerulein).The cells were harvested 3 h after treatment.Secretion rate of amylase was measured.The translocation of p-p38 MAPK to nuclei was imaged by immunofluorescence.The protein expression levels of p-p38 MAPK and TNF-α were detected by Western blotting.The activation of NF-κB was measured by electrophoretic mobility assay.RESULTS: Compared with control group, cerulein resulted in increases in the secretion rate of amylase and protein level of TNF-α (P<0.01), as well as the expression levels of p-p38 MAPK and NF-κB (P<0.01).Cerulein induced nuclear translocation of p-p38 MAPK.Compared with cerulein group, the secretion rate of amylase and protein level of TNF-α in SB203580 group decreased significantly (P<0.01).The expression of p-p38 MAPK and NF-κB also decreased greatly (P<0.05).Nuclear translocation of p-p38 MAPK was inhibited by SB203580.CONCLUSION: The p38 MAPK pathway involves in cerulein-induced pancreatic inflammatory response via regulating NF-κB.  相似文献   

10.
AIM: To investigate the effect of hypercapnia on hypoxia-induced pulmonary hypertension and the changes of lysyl oxidase (LOX) and extracellular matrix collagen cross-links in the rat. METHODS: Sprague-Dawley rats were randomly divided into 4 groups:normoxia group, hypoxia group, hypercapnia group and hypoxia+hypercapnia group. LOX activity was detected by fluorescence spectrophotometry. LOX protein expression was detected by immunohistochemistry and Western blot. The mRNA expression of LOX in the pulmonary artery was detected by real-time PCR. RESULTS: The levels of mean pulmonary artery pressure (mPAP), RV/(LV+S) and WA/TA in hypoxia group were significantly higher than those in normoxia group (P<0.01). Moreover, the levels of mPAP and RV/(LV+S) in hypoxia+hypercapnia group were significantly lower than those in hypoxia group (P<0.01). However, no significant difference of mPAP and RV/(LV+S) between hypercapnia group and normoxia group was observed. In hypoxia group, the collagen cross-links in the lung tissue was significantly higher than that in normoxia group and hypercapnia group (P<0.01). Importantly, collagen cross-links in the lung tissue of hypoxia+hypercapnia group was significantly lower than that in hypoxia group (P<0.01). There was no significant difference in collagen cross-links between hypercapnia group and normoxia group. The expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries of hypoxia group were significantly increased as compared with normoxia group (P<0.01). Furthermore, the expression of LOX at mRNA and protein levels and its activity in the pulmonary arteries in hypoxia+hypercapnia group were lower than those in hypoxia group (P<0.01). CONCLUSION: Hypoxia not only up-regulates LOX but also promotes collagen cross-linking in the rat lung, which contributes to the development of pulmonary hypertension. Hypercapnia inhibits hypoxia-induced LOX expression and collagen cross-linking, therefore impairing the progress in hypoxia-induced pulmonary hypertension.  相似文献   

11.
AIM:We used an animal model of chronic hypoxia to mimic right ventricular hypertrophy and try to study the potential mechanism of myocardium apoptosis of right heart in rat under chronic hypoxia. METHODS: Rat hypoxia models were established by exposing the rats to normobaric chronic hypoxia (oxygen levels were maintained at 9.5%-10.5%). Sixty rats were separated into two groups: one exposed to hypoxia and the other serving as control. Ten rats, randomly selected from each group were killed at 14, 21, 28 d after hypoxia. The apoptosis was determined. The changes of RV weight to left ventricle and interventricular septum weight ratio［RV/(LV+S)］, the RV weight to body weight ratio (RV/BW) were also observed. The β-MHC, bcl-2 and bad mRNA levels in right ventricle were detected by semi-quantitative RT-PCR assays and expression of β-MHC, Bcl-2 and Bad protein levels were detected by Western blotting.RESULTS: The RV/(LV+S), RV/BW and apoptosis index in chronic hypoxia group were higher than those in normal control group (P<0.01). The results of RT-PCR and Western blotting showed that β-MHC mRNA levels and protein levels in chronic hypoxia group were higher than those in normal control group (P<0.01). The rate of apoptosis, the RV/(LV+S), RV/BW and the expression of β-MHC in hypoxia group all increased with time. The bcl-2 mRNA and Bcl-2 protein expressions in chronic hypoxia group were lower compared with control group at 14, 21 and 28 d (P<0.05). In contrast, no significant change of bad mRNA and Bad protein expressions in chronic hypoxia group were observed compared with control group (P>0.05). Finally, a decreased bcl-2/bad〖STBZ〗 ratio in chronic hypoxia group was found compared with control group (P<0.05). Both the expression of bcl-2 and the bcl-2/bad ratio decreased with time (P<0.05).CONCLUSION:These data demonstrate that chronic hypoxia may induce right ventricular hypertrophy, as well as cardiomyocytes apoptosis. Furthermore, apoptosis in hypertrophic cardiomyocytes induced by hypoxia is mainly due to the inhibition of bcl-2 expression and decrease of bcl-2/bad ratio.  相似文献   

12.
AIM: To investigate whether the opening of ATP-sensitive K+(KATP) channels protects H9c2 cardiac cells against high glucose(HG)-induced injury and inflammation by inhibiting the Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB) pathway. METHODS: The protein levels of TLR4 and NF-κB p65 were determined by Western blot. The levels of interleukin-1β(IL-1β) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The cell viability was measured by CCK-8 assay. Mitochondrial membrane potential(MMP) was examined by rhodamine 123(Rh 123) staining followed by photofluorography. The intracellular levels of reactive oxygen species(ROS) were detected by 2', 7'-dichlorfluorescein- diacetate(DCFH-DA) staining followed by photofluorography. The number of apoptotic cells was observed by Hoechst 33258 nuclear staining followed by photofluorography. RESULTS: After the H9c2 cardiac cells were treated with HG(35 mmol/L glucose) for 24 h, the protein levels of TLR4 and phosphorylated NF-κB p65(p-NF-κB p65) were significantly increased. Pretreatment of the cells with 100 μmol/L diazoxide(DZ, a KATP channel opener) for 30 min before exposure to HG considerably blocked the up-regulation of the TLR4 and p-NF-κB protein levels induced by HG. Moreover, co-treatment of the cells with 30 μmol/L TAK-242(an inhibitor of TLR4) obviously inhibited the HG-induced up-regulation of the p-NF-κB p65 protein level. On the other hand, pretreatment of the cells with 100 μmol/L DZ had a clear myocardial protection effect, which attenuated the HG-induced cytotoxicity, inflammatory response, mitochondrial damage, oxidative stress and apoptosis, evidenced by an increase in the cell viability, and decreases in the levels of IL-1β and TNF-α, MMP loss, ROS generation and the number of apoptotic cells. Similarly, co-treatment of H9c2 cardiac cells with 30 μmol/L TAK-242 or 100 μmol/L PDTC(an inhibitor of NF-κB) and HG for 24 h also obviously reduced the above injuries and inflammation induced by HG.CONCLUSION: The opening of KATP channels protects H9c2 cardiac cells against HG-induced injury and inflammation by inhibiting the TLR4/NF-κB pathway.  相似文献   

13.
AIM: To study the effect of chronic hypoxic hypercapnia on expression of heme oxygenase-1 (HO-1). METHODS: Sprague-Dawley rats were randomly divided into three groups: control group(A),hypoxic hypercapnic group(B), hypoxic hypercapnia+hemin group(C). HO-1 and HO-1 mRNA were observed in pulmonary arterioles by the technique of immunohistochemistry and in situ hybridization. RESULTS: ① mPAP and weight ratio of right ventricle (RV) to left ventricle plus septum (LV+S) were significantly higher in rats of B group than those of A and C group (P<0.01). Differences of mCAP were not significant in three groups(P>0.05). ② Blood CO concentration was significantly higher in rats of B group than that of A group (P<0.01), it was much higher in C group than that of B group(P<0.01). ③ Light microscopy showed that vessel well area/total area (WA/TA), density of medial smooth muscle cell (SMC) and media thickness of pulmonary arterioles were much higher in rats of B group than those of A and C group (P<0.01). ④ The observation by electron microscopy showed proliferation of medial smooth muscle cells and collageous fibers of pulmonary arterioles in rats of B group, hemin could reverse the changes mentioned above. ⑤ HO-1 and HO-1 mRNA in pulmonary arterioles was significantly higher in rats of B group than those of A group(P<0.01), and they were significantly higher in rats of C group than those of B group (P<0.01). CONCLUSION: Expression of HO-1 mRNA and HO-1 in pulmonary arterioles was enhanced by hypoxic hypercapnia. Hemin partly inhibited pulmonary hypertension and pulmonary vessel remodeling by enhancing the expression of HO-1 mRNA and HO-1.  相似文献   

14.
AIM: To investigate the effect of chronic hypoxia-hypercapnia and L-arginine (L-Arg) liposome on L-Arg transport in rats pulmonary artery. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups, normal control group (NC), chronic hypoxia-hypercapnia group (HH), chronic hypoxia- hypercapnia group+L-Arg (HL) and chronic hypoxia-hypercapnia group+L-Arg liposome (HP). Changes in pulmonary artery L-Arg transport and pulmonary arterial microscopy were observed. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and weight ratio of right ventricle to left ventricle and septum (RV/LV+S) in HH group were higher than those in NC group, and in HP group was lower than that in HH group and HL group, but there was no significant difference between HL group and HH group; (2) At 0.005 mmol/L, 0.01mmol/L, 0.02mmol/L, 0.05 mmol/L, 0.1 mmol/L and 0.2mmol/L concentration of L-Arg, the velocity of L-Arg transport in HH group was lower than that in NC group, and in HL group higher than in HH group, and in HP group was much higher than that in HH group and in HL group. (3) Light microscopy showed that vessel well area/total area (WA/TA) and media thickness of pulmonary arterioles (PAMT) were much higher in rats of HH group than those in NC group, WA/TA and PAMT in HP group were obviously improved. CONCLUSION: The above results indicated that there existed a functional disturbance in L-Arg transport of pulmonary artery in rats chronically exposed to hypoxia-hypercapnia, and it was obviously enhanced when liposome was used as L-Arg carrier. Thus, it appears that liposome-L-Arg may have clinical perspective in the treatment of chronic hypoxic pulmonary hypertension.  相似文献   

15.
AIM:To investigate the role of NF-κB in diabetic neuropathy. METHODS:The diabetic rats were induced by intraperitoneal injection of streptozocin (STZ). The pain behavior test was used to detect the mechanical and thermal withdraw threshold of the rats’ bilateral hind paws. The protein levels of p-NF-κB and t-NF-κB in the rats’ L4 and L5 dorsal root ganglions (DRG) were determined by Western blotting. The expression of Nav1.7 in DRG of diabetic neuropathy rats with or without NF-κB inhibitor PDTC was detected by the method of immunohistochemistry. RESULTS:The mechanical and thermal withdraw threshold of bilateral hind paws in the diabetic rats was decreased from 4 weeks to 12 weeks after injection of STZ. The protein levels of p-NF-κB in L4 and L5 DRG were significantly increased in the rats with diabetic neuropathy. Intrathecal administration of NF-κB inhibitor PDTC attenuated the increase in p-NF-κB and Nav1.7 in L4 and L5 DRG. Pain behaviors were also alleviated by PDTC. CONCLUSION: The increase in p-NF-κB is closely rela-ted to the generation of diabetic neuropathy. Inhibition of NF-κB blocks pain behaviors and the over-expression of Nav1.7 in DRG.  相似文献   

16.
AIM:To investigate the effect of CD163/tumor necrosis factor-like weak inducer of apoptosis (TWEAK) pathway on atherosclerosis in mice. METHODS:APOE-/- mice and wild-type (WT) C57BL/6 mice were divided into 4 groups (8~10 weeks, n=10):APOE-/- +normal diet (ND) group, APOE-/- +western diet (WD) group, WT+ND group, and WT+WD group. Detection of blood lipid levels and oil red O staining of aorta artery were performed to confirm whether the atherosclerotic model was well established in 16 weeks after feeding. The aortic tissues were harvested to measure CD163 and TWEAK protein levels by Western blot, and immunohistochemical staining was also performed to localize CD163 and TWEAK protein expression on atherosclerotic plaque in each group. The cell experiments were conducted to study whether CD163 regulated TWEAK expression in M1 macrophages and foam cells, and the possible downstream pathway was investigated. RESULTS:The blood lipid levels and aorta oil red O staining showed that the animal model of atherosclerosis was successfully established in APOE-/- +ND group and APOE-/- +WD group. The protein level of CD163 was significantly increased in the aortic tissue in APOE-/- mice (P<0.05) as compared with C57BL/6 mice (P<0.05). Consistently, the protein level of TWEAK was also markedly higher in APOE-/- +ND group and APOE-/- +WD group than that in WT+ND group and WT+WD group (P<0.05). Immunohistochemical staining showed that CD163 was mainly expressed in the parts away from the lipid core, and TWEAK was found in all parts of the atherosclerotic plaque. CD163 significantly inhibited the protein expression of TEWAK in the M1 macrophages, and also significantly down-regulated the level of nuclear factor-κΒ (NF-κB) in the M1 macrophages and foam cells (P<0.05). CONCLUSION:The protein levels of CD163 and its ligand TWEAK are significantly increased in atherosclerotic mice. The CD163 positive macrophages are mainly located at the site far away from the lipid core, and CD163 may play an anti-atherosclerotic effect by inhibiting TWEAK/NF-κB pathway.  相似文献   

17.
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18.
AIM: To investigate the role of nuclear factor kappa B (NF-κB) inhibitor in the responsiveness of isolated pulmonary artery rings to protein kinase C (PKC) in rats with hypoxia-induced pulmonary hypertension. METHODS: The pulmonary artery rings removed endothelium were prepared from model rats with hypoxia-induced pulmonary hypertension and control rats. The effects of PKC activator PMA (0.5 μmol/L) time-response cures and NF-κB inhibitor PDTC (0-1 000 μmol/L) concentration-response cures on pulmonary artery rings were observed. The responsiveness of each ring was tested by applying a maximally effective concentration of phenylephrine (10 μmol/L). Data were calculated as relative ratio by the maximally responseness ( P0 ) setting at 100%, and the relative responseness tensions to PMA and PDTC were derived by dividing by the counts in P0. t1/2 and T show the time achieving half-maximal response and lasting maxima response to 0.5 μmol/L PMA, respectively. RESULTS: mPAP and RV/(LV+S)in hypoxia group were greater than those in control group(P<0.05).For the responseness of the artery rings to PMA of 0.5 mol/L,the relat ive tensions of hypoxia group were significantly higher(P<0.05)as compared with respective controls;mean t1/2 in hypoxia group was shorter than that in control group(P<0.05).Mean T in hypoxia group was longer than that in control group(P<0.05).For the relative tensions of the artery rings to PDTC and PMA,hypoxia group were higher than those of controls in the range of PDTC 0-100 mol/L(P<0.05);the relative tensions of two group significantly decreased beyond PDTC of 500 mol/L(P<0.05). CONCLUSIONS: The responsiveness of pulmonary artery rings to PMA was increased during hypoxia and decreased to PDTC in concentration-dependent manner. These results further suggest that changes of PKC－NF-κB signaling pathway of pulmonary artery smooth muscle cells may be involved in vasoconstriction of hypoxia-induced pulmonary hypertension.  相似文献   

19.
AIM: To investigate the changes of 5-hydroxytryptamine(5-HT)levels and to observe the expression and distribution of 5-HT1B receptors in the lung tissues of hypoxic pulmonary hypertension(HPH) rats for exploring the mechanisms of hypoxic pulmonary hypertension.METHODS: Forty male Sprague-Dawley rats were randomly divided into 4 groups: normoxia control(control group), 3 weeks hypoxia group, 4 weeks hypoxia group and 5 weeks hypoxia group. The rats in normoxia control group stayed in normal environment. The rats in 3 weeks hypoxia group, 4 weeks hypoxia group and 5 weeks hypoxia group were kept respectively in hypoxia chamber for 3 weeks, 4 weeks and 5 weeks respectively to establish the HPH animal model. After HPH was established, the mean pulmonary pressure(mPAP) and the right ventricular systolic pressure(RVSP) were recorded by a micro-catheter. RV/(LV+S) ratio was calculated to assess the right ventricular hypertrophy. 5-HT levels in plasma and lung tissues of HPH rats were measured by ELISA. The expression and distribution of 5-HT1B receptors in the lung tissues were measured by the methods of immunohistochemistry and Western blotting. RESULTS: Compared to the normoxia controls, mPAP, RVSP and RV/(LV+S)% in 3 weeks hypoxic rats increased significantly(P<0.05), and continued to increase following prolonged hypoxia. The results of ELISA showed that 5-HT levels in plasma and lung tissues of HPH rats continued to increase following prolonged hypoxic exposure(P<0.05). The 5-HT1B receptors were localized mainly in the intima of the pulmonary arteries in normal rats. Exposed to hypoxia, the immuno-reactivity for 5-HT1B receptors increased in the media of pulmonary arteries in 3 weeks hypoxic rats, particularly those bordering the adventitia. The increase in the expression of 5-HT1B receptor was observed following prolonged hypoxic exposure. The results of Western blotting showed the same changes of 5-HT1B receptor expression in the lung tissues as that of 5-HT1B immuno-reactivity in pulmonary arteries.CONCLUSION: Hypoxia induces the high 5-HT levels and the over-expression of 5-HT1B receptors in the pulmonary arteries of HPH rats, indicating the underlying mechanism of 5-HT in the development of HPH.  相似文献   

20.
AIM: To study the effect of chronic hypoxic hypercapnia on gene expression of thromboxane synthase and prostacyclin synthase in pulmonary arterioles. METHODS: Sprague-Dawley rats were randomly divided into two groups: control group and hypoxic hypercapnic group. TXS mRNA and PGI2-SmRNA were observed in pulmonary arterioles by in situ hybridization. RESULTS: mPAP, weight ratio of right ventricle (RV) to left ventricle plus septum(LV+S), contents of TXB2 and 6-keto-PGF1α in plasma and lung and TXS mRNAin pulmonary arterioles were much higher in rats of hypoxic hypercapnic group than those of control group. Differences of PGI2-SmRNA in pulmonary arterioles were not significant in two groups. Light microscopy showed hypertrophy of vessel smooth muscle cells and vessel cavity straitness were found in hypoxic hypercapnic group. CONCLUSION: Changes of gene expressions of thromboxane synthase and prostacyclin synthase and imbalance of TXA2/PGI2 may play an important role in hypoxic hypercapnic pulmonary hypertension.  相似文献   

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