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1.
HEI Zi-qing WU Wei-kang SUN Hui-lan HUANG He-qing TAN Hong-mei LUO Han-chuan 《园艺学报》2003,19(3):345-347
AIM:To observe the effects of Sini decoction on atherosclerosis(AS) and ceramide content of aorta in rabbits. METHODS:28 rabbits were randomly divided into three groups. Control group was fed with a normal diet; High cholesterol group was fed 1% cholesterol and 5% fat diet; Sini decotion+ high cholesterol group was fed 1% cholesterol and 5% fat diet plus Sini decotion (4.2 g·kg-1·d-1). At the end of study, the plaque area were measured, the atorta ceramide and cell apoptosis were also detected. RESULTS:Sini decotion diminished lipid plaque area on the aortic endothelium, reduced the levels of aorta ceramide and the apoptosis index. CONCLUSION:Sini decoction has an inhibitory effect on AS, the mechanism may be that Sini decotion reduces concentration of ceramide in aorta. 相似文献
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AIM: To study the changes of the sphingomylinase activity and ceramide content in rabbit aorta of experimental atherosclerosis and investigate the effects of emodin on them. METHODS: The qualified rabbits were fed with food containing 1% cholesterol and 5% lard for 10 weeks to establish the animal models. The concentration of cholesterol (TC) was assayed by a enzyme method. Trace-fast-test method was used to test the activity of superoxide dismutase (SOD) and motified- BAMuGuoFu methods was employed to assay the content of myocardial malondialdehyde (MDA). Radiolabeled -enzyme-tracing was used to detect the activity of the sphingomyelinase,and thin-layered scanning was conducted to analyze the content of the ceramide in aorta. RESULTS: The ceramide content in aorta and the sphingomyelinase activity were markedly increased in the rabbits with experimental atherosclerosis. The increase was positively correlated with the content of TC and MDA and negatively correlated with the activity of SOD in blood. Compared to the model animals, emodin at concentration of 5 mg·kg-1, 10 mg·kg-1 and 20 mg·kg-1 respectively reduced the area of plague on endothelium in rabbit's aortic artery and elevated the activity of SOD (P<0.05). The activity of sphingomylinase and the content of ceramide were decreased at the same time (P<0.05). 10 mg·kg-1 emodin proved to be more effective than 5 mg·kg-1 and 20 mg·kg-1 emodin (P<0.01). CONCLUSIONS: Our data suggest that atherosclerosis is related to ceramide signal transduction initiated by factors such as oxidative stress in hypercholesterolemia. The emodin prevents the development of atherosclerosis probably by interfering with the above pathway. 相似文献
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AIM: To investigate the effect of tea-polyphenols (TP) on the lipoprotein lipase (LPL) and hepatic lipase (HL) activity in atherosclerosis (AS) rabbits. METHODS: The rabbits feeding lipodiet were taken in 200 μg·g-1·d-1 TP through the experiment. The LPL and HL activity in the plasma of rabbits were detected. The LPL activity in the arteria tissue and HL activity in liver tissue were estimated with histochemistry technique. RESULTS: The LPL and HL activity in the plasma were not significantly different between premier and post experiment in AS rabbits (P＞0.05), between AS group and control group (P＞0.05). The LPL activity in the arteria tissue were not different between AS group and control group (P＞0.05). HL activity in liver tissue in AS group was significantly lower than control group (P＜0.05), but TP group was higher than AS group (P＜0.05). In TP group, the TC and LDL-c level in plasma were lower (P＜0.05), and the area of atherosclerosis plaque were smaller than those in AS group (P＜0.05). CONCLUSION: TP increased HL activity in liver tissue in AS rabbits, which correlated with decreasing the TC and LDL-c level in plasma and the area of atherosclerosis plaque. 相似文献
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AIM: To observe the level of metallothionein (MT) in liver, aorta and plasma of rabbit with atherosclerosis (AS) in order to recognize the alteration of oxidative defense system in body when AS occurred.METHODS:Preparation of AS model of rabbit induced by having high-fat diet for eight weeks; the levels of MT and malondialdehyde (MDA) were measured in the tissues of liver and aorta and plasma of rabbit.RESULTS:The MT levels in liver tissues and plasma in atherosclerotic group increased 318%(P＜0.01) and 62% (P＜0.01), compared with control group, but its level in aortic tissue in atherosclerotic group decreased 33% (P＜0.01). The MDA levels in liver, aortic and plasma in atherosclerotic group increased 95%(P＜0.01), 76%(P＜0.01) and 42%(P＜0.01), respectively, compared with control group. The changes of contents of MT in liver and plasma have relation with level of MDA in liver tissues and plasma.CONCLUSION:The alteration of MT in liver tissues and plasma in atherosclerotic rabbits may be related to lipid hyperoxidative injury. 相似文献
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AIM: To investigate the relationship between the thrombin-activatable fibrinolysis inhibitor (TAFI) level in plasma and atherosclerosis, the TAFI level in plasma and blood fat and blood clotting index.METHODS: Totally 40 healthy male Wistar rats were randomly divided into 4 groups (n=10), control group, high lipid group, high lipid +vitamin D3 overload group, and high lipid +vitamin D3+endothelium injure group by treating the animals with normal diet, high lipid, high lipid+ vitamin D overload, and high lipid+vitamin D overload+endothelium injury, respectively, for inducing three stages of AS in rats. Then, the total cholesterol (TC), total triglyeride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), and prothrombin time (PT), activated partial thromboplasin time (APTT), fibrinogen (Fib), the activity of TAFI were measured.RESULTS: TC, TG, LDL-C, Fib and the activity level of TAFI in plasma in three model groups increased gradually compared with the control (P＜0.01). HDL-C, PT and APTT in plasma of three model groups decreased gradually compared with the control (P＜0.01 or P＜0.05). The activity of TAFI in plasma had positive correlation with TG, TC and Fib.CONCLUSION: The activity of TAFI increases in the progress of atherosclerosis. The activity of TAFI in plasma has a correlation with blood fat and coagulation, which indicates that TAFI might participate in the process of atherosclerosis, and TAFI is one of etiological factors of atherosclerosis. 相似文献
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AIM: To investigate the effect of Fufang Zhenzhu Tiaozhi capsule (FTZ) on serum lipids and inflammatory factors in rabbits with abdorminal aortic restenosis after balloon angioplasty.METHODS: New Zealand white rabbits (n=30) were divided into 5 groups. Except blank control group, the rabbits in other groups were used to establish abdominal aortic endothelium exfoliative vascular stenosis model. After 4 weeks of high-fat diet feeding, the animals in restenosis model group and drug treatment groups underwent percutaneous balloon dilatation in the stenosis. The angiographic stenosis was analyzed by a two-dimensional quantitative coronary angiography workstation with a digital subtraction X-ray machine. Blood samples were taken during angiography and the profiles of serum lipids and cytokines were measured. The expression of nuclear factor-κB (NF-κB) in the blood vessels was determined by immunohistochemistry.RESULTS: Angiography confirmed that the rates of area stenosis and diameter stenosis were significantly decreased in treatment groups compared with restenosis model group (P<0.01). Compared with restenosis model group, the serum lipid profiles and cytokine concentrations in drug treatment groups were significantly decreased (P<0.05). Immunohistochemistry showed the expression of NF-κB in restenosis model group was significantly higher than that in blank control group and drug treatment groups (P<0.05).CONCLUSION: FTZ significantly reduces the blood lipids and inflammatory factors in abdominal aortic restenosis model, and the anti-inflammatory effect may be related to the regulation of NF-κB pathway to inhibit the production of various inflammatory factors. 相似文献
8.
XIONG Ming BI Yong-yi ZHANG De-ling SONG Jie YANG Hai-lu XU Yi OUYANG Jing-ping 《园艺学报》2008,24(9):1670-1675
AIM:To investigate the effects of sodium ferulate on cholesterol and triglyceride metabolism in atherosclerosis with hyperlipidemia. METHODS:The rabbit model of atherosclerosis was produced by feeding high lipid forages. RAW264.7 foam cell and HepG2 injured cell models were established by incubation with oxidized low density lipoprotein (ox-LDL). The atherosclerotic plaque area was measured, and serum lipids were detected. The cellular lipid accumulation was examined by oil red O staining. The cellular contents of total cholesterol and cholesterol ester were quantified by high performance liquid chromatography. The hepatic lipase (HL) mRNA expression was determined by RT-PCR. RESULTS:(1) Compared with hyperlipid group, the aorta atherosclerosis plaque area and the serum triglyceride level were significantly decreased in sodium ferulate-treated rabbits, but the serum cholesterol level showed little change. (2) Compared with ox-LDL group, the HL mRNA expression in HepG2 cells was enhanced significantly in sodium ferulate-treated group, but the cellular contents of total cholesterol and cholesterol ester in RAW264.7 foam cells showed little change. CONCLUSION:Sodium ferulate inhibits the formation of atherosclerotic plaque in high-cholesterol-fed rabbits aorta. This antiatherosclerotic function may reduce serum triglyceride level through enhancing the expression of HL mRNA without influencing serum cholesterol level and foam cell formation. 相似文献
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AIM: To investigate the effects of Danggui Buxue decoction (DBD) on serum vascular endothelial growth factor (VEGF) and stromal cell-derived factor 1 (SDF-1), as well as the activity of circulating endothelial progenitor cells (EPCs) in atherosclerotic rabbits. METHODS: The model of atherosclerosis was established using immune injury and fatty diet for 4 weeks in New Zealand rabbits (n=25). All modeled rabbits were randomized into 5 groups with 5 animals in each group. The rabbits in atherosclerosis group were intragastrically administered with distilled water. The rabbits in simvastatin group were treated with simvastatin at the dose of 1.7 mg/kg. The rabbits in DBD high-dose, middle-dose and low-dose treatment groups were given DBD at the doses of 6 g/kg, 3 g/kg and 1.5 g/kg, respectively. All drugs were given once a day for 2 weeks. After treatment, the levels of serum VEGF and SDF-1 were measured. The mononuclear cells isolated from the rabbit peripheral blood were cultured for 7 days in vitro, and then attached cells were cultured with both DiI-ac-LDL and FITC-UEA-1 for identification. The proliferation was detected by MTT method. The cell migration was observed using Transwell chambers. The adhesion determination and in vitro angiogenesis assay were also performed. RESULTS: Compared with atherosclerosis group, the levels of serum VEGF and SDF-1 were elevated (P<0.05), the proliferation, migration, adhesion and angiogenesis of EPCs were all improved in DBD high-dose, middle-dose treatment groups and simvastatin group (P<0.05). CONCLUSION: DBD elevates the levels of serum VEGF and SDF-1 to improve the activity of EPCs in the process of atherosclerosis. 相似文献
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AIM To observe the effect of Chaihu-Shugan decoction (CHSGD) on atherosclerosis in spontaneously hypertensive rats (SHR) and its possible mechanism. METHODS The male SHR (n =50) were randomly divided into model group (gavage of normal saline), compound kendir leaves (CKL) group (gavage of 0.5 g/kg CKL), and low-, medium- and high-dose CHSGD (CHSGD-L, CHSGD-M and CHSGD-H) groups (gavage of 2.5, 5 and 10 g/kg CHSGD, respectively), and another 10 male Wistar rats of the same origin were selected as normal control （NC) group (gavage of normal saline). The blood pressure was measured by intelligent noninvasive sphygmomanometer. The levels of blood lipids were measured by automatic biochemical analyzer. The expression of oxidative stress-related indexes, nitric oxide (NO), malondialdehyde (MDA) and superoxide dismutase (SOD), were detected by colorimetry. HE staining was used to detect the degree of atherosclerosis, and Western blot was used to detect the expression of Rho-associated kinase (ROCK)/c-Jun N-terminal kinase (JNK) signaling pathway-related proteins, RhoA, ROCK1 and JNK. RESULTS After 4 weeks of treatment, compared with NC group, the blood pressure, the serum levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in model group were significantly increased (P <0.05), and the serum levels of high-density lipoprotein cholesterol, NO and SOD were significantly decreased (P <0.05). HE staining showed that the diameter of aortas in the rats was thickened, a large number of foam cells were formed under the endothelium, and the proliferation of smooth muscle cells was observed. Compared with model group, the blood pressure, the serum levels of TG, TC, LDL-C and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in CKL, CHSGD-L, CHSGD-M and CHSGD-H groups were significantly decreased (P <0.05), and the serum levels of NO and SOD were significantly increased (P <0.05). HE staining showed that the structure of each layer of rat aortas gradually returned to normal, the vascular cells were in good order, and the inflammatory cell infiltration was slight. Compared with CKL group, the blood pressure, the serum levels of TG, TC, LDL-C and MDA, and the protein expression of RhoA, ROCK1 and JNK in aortic tissues of the rats in CHSGD-L and CHSGD-M groups were significantly increased (P <0.05), and the serum levels of NO and SOD were significantly decreased (P <0.05). No significant difference of the above indexes between CHSGD-H group and CKL group was observed (P >0.05). CONCLUSION Chaihu-Shugan decoction may attenuate the oxidative stress response via inhibition of ROCK/JNK signaling pathway, thus alleviating the symptoms of atherosclerosis in SHR. 相似文献
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AIM: To investigate the antioxidant status and the oxidative damage of cellular macromolecules in patients with Graves' disease. METHODS: Fasting plasma level of total antioxidant capacity (TAC), and the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in 31 patients with untreated Graves' disease and 31 treated Graves' disease. DNA damage of peripheral blood mononuclear cell (PBMC) was detected by single cell gel electrophoresis assay (expressed in comet percentage). In addition, thiol group (SH) and malondialdehyde (MDA) were measured. 31 age-matched healthy subjects were studied as a control group. RESULTS: Plasma TAC, SOD and GSH-Px were significantly lower in patients with untreated Graves' disease compared to the controls (P＜0.05, P＜0.01). The comet percentage of PBMC and the content of MDA in plasma from patients with untreated Graves' disease were significantly higher than those from the controls (P＜0.01), whereas the level of SH was decreased in patients with untreated Graves' disease (P＜0.01). Threatment with methimazole led to an improvement in oxidative damage indices and antioxidant potential parameters. But they still did not turn to normal. The comet percentage of PBMC was negatively correlated with the level of TAC (r＝-0.599, -0.429, P＜0.01, P＜0.05); and was positively correlated with the level of MDA (r＝0.463, 0.402, P＜0.01, P＜0.05) in Graves' disease. CONCLUSION: The oxidation-antioxidation imbalance and the oxidative damage of cellular macromolecules are involved in the pathogenesis of Graves' disease. 相似文献
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AIM: To study the effect of crocin on the mobilization of endothelial progenitor cells (EPCs) in the peripheral blood of the mice with carotid arterial injury and its mechanism.METHODS: The carotid artery injury model of the C57BL/6 mice was established by the method of wire injury. The animals were divided into sham operation group, saline-treated model group, and low dose, medium dose and high dose (10, 50 and 100 μmol·kg-1·L-1, respectively) of crocin treatment groups. The mobilization of the EPCs in peripheral blood of the mice with carotid artery injury was detected by flow cytometry at 3 d. The changes of vascular endothelial growth factor (VEGF), stromal-derived factor-1 (SDF-1), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF) and matrix metalloproteinase-9 (MMP-9) in the peripheral blood of the mice with carotid artery injury were detected by enzyme-linked immunosorbent assay at 7 d. The vascular re-endothelialization and intimal hyperplasia of the mice with carotid artery injury were detected by Evans blue and hematoxylin-eosin staining. At the same time, real-time PCR was used to detect the mRNA expression of vascular repair factor-related receptors, vascular endothelial growth factor receotor-2 (VEGFR-2), CXC chemokine receptor-4 (CXCR4), basic fibroblast growth factor receptor (bFGFR) and epidermal growth factor receptor (EGFR), in the injured segments of carotid arteries.RESULTS: Compared with sham group, the EPCs mobilization and the content of vascular repair factors VEGF, SDF-1, bFGF, EGF and MMP-9 in peripheral blood were increased in model group (P<0.05). The area of vascular endothelium was decreased, while the area of intimal hyperplasia and the ratio of intimal to medial membrane area were increased significantly (P<0.05). The expression levels of VEGFR-2, CXCR4, bFGFR and EGFR were also increased in the injured segments of carotid arteries (P<0.05). Compared with model group, the EPCs mobilization and the content of vascular repair factors VEGF, SDF-1, bFGF, EGF and MMP-9 in peripheral blood were significantly increased in different concentrations of crocin-treated mice with carotid artery injury (P<0.05). The area of vascular endothelium was gradually increased, while the area of intimal hyperplasia and the ratio of intimal to medial membrane area were gradually decreased (P<0.05). The expression levels of VEGFR-2, CXCR4, bFGFR and EGFR were also gradually increased in the injured segments of cartid arteries (P<0.05).CONCLUSION: Crocin promotes the mobilization of EPCs and the re-endothelialization of damaged blood vessels in the mice with carotid artery injury, thus repairing the injured vasculature. 相似文献
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AIM: To observe the effect of thichosanthes injection on the expression of proliferating cell nuclear antigen (PCNA) of vascular smooth muscle cell (SMC). METHODS: The expression of PCNA of cultured rabbit aortic SMC was examined with LSAB immunohistochemical technique, and [3H]-thymidine( [3H]-TdR) incorporation data of SMC and the contents of superoxide dismutase (SOD), lipid peroxide (LPO), prostacyclin (PGI2) and cyclic AMP (cAMP) in medium were simultaneously determined. RESULTS: Thichosanthes injection has an effects of increasing SOD activity, decreasing LPO, elevating PGI2 and cAMP, reducing [3H]-TdR incorporation and expression of PCNA (all P＜0.05,P＜0.01). CONCLUSION: Thichosanthes could inhibit SMC proliferation. 相似文献
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CHEN Wen-qiang ZHANG Yun ZHANG Mei JI Xiao-ping LIN Chen ZHU Yong-feng SANG Xue-dong 《园艺学报》2005,21(5):838-843
AIM: To study the apoptotic role of wild-type p53 in induction of plaque instability in atherosclerotic rabbits. METHODS: Fifty-four New Zealand White rabbits underwent balloon-induced abdominal aortic wall injury and then were fed on a diet of 1% cholesterol. At the end of the eighth week, the rabbits were randomly divided into two groups: group A and group B. Recombinant adenovirus carrying p53 and β-galactosidase (LacZ) genes were injected in group A and B, respectively. Two weeks later, 10 rabbits each in group A and B was killed and the remaining rabbits all underwent pharmacological triggering with injection of Chinese Russell's viper venom and histamine. RESULTS: Compared with group B, p53 gene over-expression in group A resulted in a marked increase in number of positive apoptotic cells (2.5%±0.8% vs 1.0%±0.3%, P<0.05) and a significant decrease in vascular smooth muscle cells (47.5%±6.8% vs 80.4%±10.6%, P<0.01), the thickness of the fibrous cap ［(132.9±56.7）μm vs （181.8±59.7） μm, P<0.05］ and the cap/intima-media ratio (0.20±0.18 vs 0.21±0.11, P<0.05). CONCLUSION: Transfer of human wild-type p53 genes effectively promotes apoptosis of VSMCs in atherosclerotic plaques, which makes the plaques vulnerable to rupture. 相似文献
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AIM: To observe the changes of plasma oxidized low density lipoprotein(oxLDL) levels of ovariectomized cholesterol-fed rabbits with or without 17β-estradiol(E2) replacement therapy.METHODS: All rabbits were ovariectomized and fed standard chow supplemented with 1.5% cholesterol for 14 weeks. Two weeks after operation, the rabbits were randomly assigned to four groups. Three groups were treated with E2 1 mg, 2 mg, 4 mg respectively, the other group served as control. Serum superoxide dismutase (SOD) levels and plasma oxLDL levels were measured at 0, 3, 8, 12 weeks after hormone replacement therapy. The aortic atherosclerotic lesion areas were determined by computer. RESULTS: We found that there were striking increase of serum SOD levels ( P<0.05 ) and significant decrease in both the plasma oxLDL levels and the aortic atherosclerotic lesion areas ( P<0.01 respectively). Moreover, a positive correlation was found between plasma oxLDL levels and the areas of atherosclerotic plaque in all rabbits. CONCLUSIONS: Estrogen attenuates atherogenesis in cholesterol-fed ovariectomized rabbits. And this beneficial effect of E2 may be duo to its lowering of plasma oxLDL level. 相似文献
17.
ZHANG Dai-juan LIU Tong-mei CUI Xiao-dong LIU Jiang-yue GUO Jun-tang WANG Jian-ying YE Du-yun 《园艺学报》2010,26(9):1700-1703
AIM: To observe the preventive effect of 3,4-dihydroxyacetophenone (DHAP) on atherosclerosis (AS) and the role of visfatin expression in ApoE(-/-) mice.METHODS: Eight-week-old normal mice were used in normal control group (n=8). Eight-week-old male ApoE (-/-) mice were randomly divided into 3 groups: AS group (n= 8, im. NS), DHAP treatment group (n=8, im. DHAP 10 mg·kg-1·d-1) and simvastatin treatment group (n=8, im. simvastatin 10 mg·kg-1·d-1). All mice were fed with Western diet (21% fat, 0.15% cholesterol) for 12 weeks. The blood samples were collected and the concentrations of blood lipids and visfatin were detected. The frozen sections of aortic root were stained with oil red O. The visfatin in atherosclerotic plaques at aortic roots was examined by Western blotting. The structures of smooth muscle cells and endothelial cells were observed under electron microscope. RESULTS: In DHAP-treated mice, the concentrations of visfatin, TG and TC were decreased, the formation of AS plaque was reduced, the injuries of smooth muscle cells and endothelia cells were attenuated. Visfatin was also decreased at atherosclerosis plaque in DHAP-treated mice.CONCLUSION: DHAP effectively prevents and treats AS by inhibiting the production of visfatin and reducing lipid. 相似文献
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AIM:To evaluate the effects of interfer α-2b (IFN α-2b ) on atherosclerosis(AS).METHODS:Thirty normal male rabbits were randomly divided into five groups:normal controlgroup(NCgroup,n＝6),atherosclerosisgroup(AS group, n=6),virus (herpesvirus Ⅰ,HSV-Ⅰ)infected atherosclerosis group(V group,n＝6), interferon (interferon α-2b) intervented atherosclerosis group (IFN-Ⅰgroup,n＝6),interferon intervented and virus infected atherosclerosis group (IFN-Ⅱ group, n＝6). Serum lipids were measured and the thoracic aortas were sampled for histopathological, immunohistochemical and in situ hybridization study.RESULTS:The aorta atherosclerosis areas of NC, IFN-Ⅰ and IFN-Ⅱ groups were lower than that of AS group significantly, respectively, and the area of AS group was lower than that of V group (P＜0.05). Platelet-derived growth factor B-chain (PDGF-β) expression was reduced both in IFN-Ⅰand IFN-Ⅱ groups(P＜0.05).CONCLUSIONS:Our data provide evidence that virus could cause atherosclerosis, and the AS formation could be inhibited by IFN α-2b through its antivirus effect and inhibitory effect on PDGF-β and VSMC proliferation. 相似文献
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AIM: To study the relationship between the effects of polysaccharide L01 extracted from laminaria japonica aresch on platelet activation and endothelial cells. METHODS: A rat model of endothelial injury was established via injecting adrenaline. The percentage of platelet adhesion was evaluated by filtration method, the activation of platelet aggregation was observed on a glass plate with collodion membrane, the content of vWF in rat plasma was measured by ELISA, the damaged degree of aortic vascular endothelial was evaluated by immunity histochemistry. RESULTS: The percentage of platelet adhesion and aggregation in model group were higher than those in NS group from the 3th and 4th day during the model made (P<0.05, P<0.01). The percentage in both L01 high-dose group (50 mg/kg) and low-dose group (10 mg/kg) at the 4th and 5th day was lower than that in model group (P<0.05, P<0.01). The content of vWF in rat plasma in model group was higher than that in NS group and in L01 high-dose group at 4th day (P<0.05). The same results were presented by the comparison among model group and NS group, both L01 high-dose group and low-dose group at the 5th (P<0.05). The measure of intact endodermis lengths (μm) stained by immunohistochemistry demonstrated that the length in model group was shorter than that in NS group (P<0.05), whereas the length in L01 high-dose group and low-dose group was obviously longer than that in model group (P<0.05) at the 4th and 5th day. CONCLUSION: The inhibitory effect of L01 on platelet activation may be related with its protective effect on vascular endothelial cells. 相似文献
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AIM:To investigate the effect of shikonin on the apoptosis and oxidative stress induced by high concentration of glucose in vascular endothelial cells. METHODS:Rat thoracic aortic endothelial cells were randomly divided into 5 groups:normal control group (with glucose at concentration of 5.5 mmol/L in cell culture medium), high glucose group (with glucose at concentration of 33 mmol/L in cell culture medium), high glucose+low shikonin group (with glucose at concentration of 33 mmol/L and shikonin at concentration of 0.1 μmol/L in cell culture medium), high glucose+medium shikonin group (with glucose at concentration of 33 mmol/L and shikonin at concentration of 1 μmol/L in cell culture medium), and high glucose+high shikonin group (with glucose at concentration of 33 mmol/L and shikonin at concentration of 10 μmol/L in cell culture medium). After treatments, the cell viability was measured by CCK-8 assay and cell apoptotic rate was analyzed by flow cytometry. In addition, the status of oxidative stress was evaluated by determining the levels of malondialdehyde (MDA), reactive oxygen species (ROS), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). The activation of Nrf2/HO-1 signaling pathway was determined by Western blot. RESULTS:Compared with high glucose group, shikonin reversed high glucose-induced decrease in cell viability and increase in apoptosis in a concentration-dependent manner. High concentration of glucose induced high levels of MDA and ROS, while decreased the levels of SOD and GSH-Px. However, after treatment with shikonin, the contents of MDA and ROS were decreased, while the activities of SOD and GSH-Px were increased as compared with high glucose group. Furthermore, the high concentration of glucose up-regulated the protein levels of cleaved caspase-3, HO-1 and Nrf2 (nuclear). Compared with high glucose group, the protein levels of cleaved caspase-3, HO-1 and Nrf2 (nuclear) were partly decreased after treatment with shikonin. CONCLUSION:Shikonin alleviates high glucose-induced vascular endothelial cell apoptosis. Its mechanism may be related to activation of Nrf2/HO-1 signaling pathway and down-regulation of oxidative stress in vascular endothelial cells. 相似文献