白藜芦醇在高脂饮食诱导ApoE基因敲除小鼠动脉粥样硬化形成中的作用及其相关机制研究

The effect of resveratrol on high-fat diet-induced atherosclerosis in ApoE-/-mice

目的:探讨白藜芦醇对高脂饮食诱导载脂蛋白E基因敲除(ApoE-/-)小鼠动脉粥样硬化形成的影响及其相关机制。方法:本实验分为4组,正常对照组为ApoE-/-小鼠给予普通饲料喂养。此外,高脂饲料喂养ApoE-/-小鼠16周,构建动脉粥样硬化小鼠模型,并随机分为模型组(Vehicle组,灌胃给予1ml/d 0.9%氯化钠溶液)、白藜芦醇低剂量组(灌胃给予白藜芦醇20mg·kg^(-1)·d^(-1))、高剂量组(灌胃给予白藜芦醇40mg·kg-1·d^(-1)白藜芦醇)。灌胃8周后造模完成,采集血清,分离主动脉。油红O染色检测小鼠主动脉粥样硬化斑块大小;酶联免疫吸附试验(ELISA)法检测血清中IL-8/CXCL8的水平;实时荧光定量PCR和免疫印迹法分别检测主动脉组织中CXCR2的mRNA表达水平以及PCNA、MEF2a的蛋白表达水平。结果:与正常组相比,给予高脂饮食后,模型组小鼠体重明显增加,而白藜芦醇处理可明显抑制小鼠体重的增加;与模型组小鼠比较,白藜芦醇处理能降低小鼠的动脉粥样硬化斑块面积大小,降低血清中IL-8/CXCL8的水平、CXCR2的mRNA表达水平以及PCNA、MEF2a的蛋白表达水平,且与白藜芦醇的剂量呈正相关。结论:白藜芦醇可有效缓解动脉粥样硬化的形成,可能与调控ApoE-/-小鼠的CXCR2的mRNA和PCNA、MEF2a蛋白的表达有关。

Objective：To investigate the effect of resveratrol on high-fat diet-induced atherosclerosis in ApoE-/-mice and its possible mechanisms.Method：ApoE-/-mice were fed with high-fat diet for 16 weeks to induce atherosclerosis models and then were administered with resveratrol via oral gavage once daily at dose of 20 or 40mg/kg body weight for 8weeks.After 24 weeks,mice serum was harvested and aortas were carefully isolated.The formation of atherosclerotic plaque was analyzed by oil red O staining.The levels of IL-8/CXCL8 in serum were detected by ELISA assay.The expressions of CXCR2,PCNA and MEF2awere determined by qPCR and Western blot,respectively.Result：Compared with normal diet mice,high-fat diet significantly increased the body weight of ApoE-/mice.The increased body weight was marked attenuated after resveratrol treatment.Moreover,resveratrol dose-dependently inhibited high-diet-induced the increase in atherosclerotic plaque area,the level of IL-8/CXCL8,and the expression of CXCR2,PCNA and MEF2a.Conclusion：Resveratrol attenuates the formation of atherosclerotic plaque may through inhibiting the expressions of CXCR2,PCNA and MEF2a.