菲牛蛭素对载脂蛋白E基因敲除小鼠动脉粥样硬化斑块的干预作用

发布时间：2019-05-24 10:52

【摘要】：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)mmol·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P0.01)。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P0.01)。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。
[Abstract]:Objective to study the effect of phenanthrene on atherosclerosis and plaques in apolipoprotein E knockout (ApoE~ (- / -) mice. Methods male ApoE~ (- / -) mice fed with high fat diet were randomly divided into three groups according to body weight: model group, The control group (treated with simvastatin 3mg kg~ (- 1) d ~ (- 1) and the experimental group (treated with 400 U kg~ (- 1) d ~ (- 1) were given intraabdominal injection of phenanthrene (- 1) d ~ (- 1). C57BL/6J mice were also set as normal group (without any treatment). After 10 weeks of administration, the levels of serum triacylglycerol (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured by automatic biochemical instrument. The expression of aortic vascular marker CD34 protein, vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR-2) was detected by immunohistochemistry. Results after administration, the serum TG of the model group, the control group and the experimental group were (1.57 卤0.12), (1.10 卤0.21), (0.95 卤0.20) mmol 路L ~ (- 1), respectively. The TC of the three groups was (19.93 卤2.24), (14.47 卤1.30), (11.90 卤2.38) mmol 路L ~ (- 1), respectively. The LDL-C of the three groups was (17.24 卤1.52), (13.94 卤1.46), (10.02 卤2.14) mmol 路L ~ (- 1), respectively. The HDL-C of the three groups was (4.05 卤1.81), (4.62 卤0.50), (3.38 卤0.24) mmol 路L ~ (- 1), which was significantly different from that of the model group (all P 0.01). In the model group, the relative contents of plaque collagen in the control group and the experimental group were (21.48 卤2.44)%, (37.12 卤3.33)% and (51.60 卤2.47)%, respectively. The contents of CD34 protein in these three groups were (11.02 卤1.64)%, (6.82 卤0.66)%, (4.56 卤0.59)%, and (22.13 卤2.04)%, (16.20 卤0.65)%, (11.16 卤0.82)%, respectively. The expression of VEGFR-2 protein in the three groups was (17.90 卤0.73)%, (15.11 卤0.52)% and (10.56 卤0.60)%, respectively, which was significantly different from that in the model group (all P 0.01). Conclusion phenanthrene can improve atherosclerosis and stabilize atherosclerotic plaques in ApoE~ (- / -) mice. The mechanism may be related to the decrease of VEGF and VEGFR-2 expression and the inhibition of plaque microvessel regeneration.
【作者单位】：广西医科大学药学院;广西科学院生物研究所;南宁市动物疫病预防控制中心;广西医科大学第二附属医院药学部;
【基金】：广西科学研究与技术开发基金资助项目(桂科攻0424008-2F)
【分类号】：R285.5

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