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目的 研究菲牛蛭素对载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化及斑块的干预作用.方法 按照体重将高脂饲料喂养的雄性ApoE-/-小鼠随机分为3组:模型组、对照组(给予辛伐他汀3mg· kg-1·d-1灌胃)和实验组(给予菲牛蛭素400 U·kg-1·d-1腹腔注射);另设C57BL/6J小鼠为正常组(不予任何处理).给药10周后,全自动生化仪检测各组小鼠血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)的水平,以免疫组化法检测主动脉血管标记物CD34蛋白、血管内皮生长因子(VEGF)及血管内皮生长因子受体(VEGFR-2)的表达.结果 给药后,模型组、对照组和实验组血清TG分别为(1.57±0.12),(1.10±0.21),(0.95±0.20) mmol·L-1;这3组的TC分别为(19.93±2.24),(14.47±1.30),(11.90±2.38) mmol·L-1;这3组的LDL-C分别为(17 24±1.52),(13.94 ±1.46),(10.02±2.14) mmo1·L-1;这3组的HDL-C分别为(4.05±1.81),(4.62±0.50),(3.38±0.24) mmol·L-1,与模型组相比,实验组差异均有统计学意义(均P＜0.01).模型组、对照组和实验组的斑块胶原相对含量分别为(21.48±2.44)％,(37.12±3.33)％,(51.60±2.47)％;这3组的CD34蛋白含量分别为(11.02±1.64)％,(6.82±0.66)％,(4.56±0.59)％;这3组的VEGF蛋白分别为(22.13±2.04)％,(16.20±0.65)％,(11.16 ±0.82)％;这3组的VEGFR-2蛋白表达分别为(17.90±0.73)％,(15.11±0.52)％,(10.56 ±0.60)％;与模型组相比,实验组差异均有统计学意义(均P＜0.01).结论 菲牛蛭素可改善ApoE-/-小鼠动脉粥样硬化,稳定粥样斑块,其机制可能与减少VEGF和VEGFR-2表达、抑制斑块微血管新生有关.“,”Objective To study the interventional effect of Bufrudin on aorta atherosclerosis and angiogenesis in apolipoprotein E gene knockout (ApoE-/-) mice.Methods Male ApoE-/-mice on high fat diet,were randomly divided into three groups:model group,control group,experimental group.Experimental group were given Bufrudin (400 U · kg-1 · d-1),control group were given simvastatin (3 mg · kg-1 · d-1).And C57BL/6J mice fed with common diet was served as normal group.After ten weeks,mice blood was collected and serum levels of triglyceride (TG),total cholesterol(TC),low-density lipoprotein cholesterol (LDL-C),high density lipoprotein cholesterol (HDL-C) concentrations were measured.The expression of CD34 protein,vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR-2) were detected by immunohistochemstry.Results After administraiton,the serum content of TG in model group,control group and experimental group were (1.57 ± 0.12),(1.10 ± 0.21),(0.95 ±0.20) mmol · L-1,respectively;TC in above three groups were (19.93 ± 2.24),(14.47 ± t.30),(11.90 ± 2.38) mmol · L-1,respectively;LDL-C in above three groups were (17.24 ± 1.52),(13.94 ± 1.46),(10.02 ±2.14) mmol · L-1,respectively;HDL-C in above three groups were (4.05 ± 1.81),(4.62 ± 0.50),(3.38 ± 0.24) mmol · L-1,respectively.Compared with model group,the serum content of TG,TC,LDL-C,HDL-C in experimental group were significantly decreased (all P ＜ 0.01).The content of collagen in model group,control group and experimental group were (21.48 ± 2.44)％,(37.12 ± 3.33)％,(51.60 ± 2.47)％;the expression of CD34 protein in above three groups were (11.02 ± 1.64) ％,(6.82 ± 0.66) ％,(4.56 ± 0.59) ％;the expression of VEGf prtein in above three groups were (22.13 ± 2.04) ％,(16.20 ± 0.65) ％,(1 1.16 ± 0.82) ％;and the expression of VEGfR-2 in above three groups were (17.90 ± 0.73)％,(15.11 ± 0.52) ％,(10.56 ± 0.60) ％,respectively.Compared with model group,the content of collagen in experimental group was increased,and the expression of CD34 protein in experimental group was decreased,all about with statistical difference (all P ＜ 0.05).Conclusion Bufrudin attenuate atherosclerosis disease and stabilize the atherosclerotic plaque in ApoE-/-mice likely through suppressing the expression of VEGF and VEGFR-2.