糖尿病性动脉粥样硬化大鼠血浆VEGF及TGF-β1表达水平的改变和辛伐他汀的保护作用
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Expression of VEGF and TGF-β1 on Diabetic Atherosclerosis in Rats and the Mechanism and Protective Effects of Simvastatin
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    目的 观察糖尿病性动脉粥样硬化大鼠血浆血管内皮生长因子(VEGF)、转化生长因子β1(TGF-β1)表达水平的改变及辛伐他汀的保护作用。方法 将雄性SD大鼠随机分为正常对照组(n=8)、正常干预组(n=8)、模型组(n=18)、模型干预组(n=16)。干预组给予辛伐他汀溶液20 mg/(kg·d)灌胃,蒸馏水20 mL/(kg·d)灌胃作为正常对照组。采用链脲霉素+维生素D3+高脂高胆固醇饮食建立糖尿病动脉粥样硬化大鼠模型。测定各组大鼠空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)、空腹胰岛素(FINS),并计算稳态模型胰岛素抵抗指数(HOMA-IR),酶联免疫吸附法检测血浆VEGF、TGF-β1含量,免疫组织化学法检测动脉VEGF表达水平。结果 与正常对照组相比,干预组TGF-β1显著增高(P<0.01),模型组FPG、TC、TG、LDL、HDL、FINS、VEGF、TGF-β1显著增高(P<0.05,P<0.01);与模型组相比,干预组FPG、TC、TG、LDL、HDL、VEGF显著降低(P<0.01,P<0.05),TGF-β1显著增高(P<0.01)。相关分析显示,VEGF与体重、FINS呈负相关,与TC、TG、LDL、FPG、HOMA-IR呈正相关;TGF-β1与TC、LDL、FPG呈负相关。多元线性逐步回归显示,FPG、TG是影响血浆VEGF水平的独立危险因素。结论 VEGF、TGF-β1可能参与糖尿病性动脉粥样硬化的发生,辛伐他汀能下调VEGF、上调TGF-β1表达,并对糖尿病性动脉粥样硬化发挥保护作用。

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    Aim To investigate the expression of vascular endothelial growth factor (VEGF) and transforming growth factor-β1 (TGF-β1) on diabetic atherosclerosis in rats and the mechanism and protective effects of simvastatin.Methods SD rats were randomized into normal control group (n=8), normal intervention group (n=8), model group (n=18) and model intervention group (n=16). Intervention groups were perfused with simvastatin at 20 mg/(kg·d), and the control groups were given distilled water [20 mL/(kg·d)] instead. The diabetic atherosclerosis model was established by streptozotocin (STZ)+vitamin D3 (VitD3)+high-fat and high-cholesterol diet. The contents of fasting plasma glucose (FPG), total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), fasting insulin (FINS) were detected, and insulin resistance homeostasis (HOMA-IR) was calculated. Plasma VEGF and plasma TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA). The expression of VEGF on aortic was evaluated by immunohistochemical method. Results Compared with normal control group, TGF-β1 was significantly increased in intervention group (P<0.01), and FPG, TC, TG, LDL, HDL, FINS, VEGF and TGF-β1 were significantly increased in model group (P<0.01, P<0.05). Compared with model group, FPG, TC, TG, LDL, HDL and VEGF were significantly decreased (P<0.01, P<0.05), and TGF-β1 was significantly higher in intervention group (P<0.01). In correlation analysis, VEGF showed a negative correlation with body weight and FINS, and had a positive correlation with TC, TG, LDL, FPG and HOMA-IR. TGF-β1 showed a negative correlation with TC, LDL and FPG. In a stepwise multiple regression analysis, FPG and TC were independent risk factors for plasma VEGF level. Conclusions VEGF and TGF-β1 may participate in the occurrence of diabetic atherosclerosis. Simvastatin can decrease the level of VEGF and increase the expression of TGF-β1, and has a significant protective effect on diabetic atherosclerosis.

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王婉秋,孙 侃,靳 瑾,周 婷.糖尿病性动脉粥样硬化大鼠血浆VEGF及TGF-β1表达水平的改变和辛伐他汀的保护作用[J].中国动脉硬化杂志,2014,22(9):929~933.

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  • 收稿日期:2014-04-04
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