摘要
目的 基于mTOR/ULK1自噬信号通路探讨绞股蓝总甙改善动脉粥样硬化模型小鼠主动脉脂质沉积的作用机制。方法 30只健康ApoE^（-/-）小鼠随机分为模型对照组、绞股蓝总甙组和辛伐他汀组,每组10只。10只C57BL/6J小鼠作为正常组。模型对照组、绞股蓝总甙组和辛伐他汀组采用高脂饲料喂养4周,绞股蓝总甙组和辛伐他汀组分别采用绞股蓝总甙2.973 g/（kg·d）、辛伐他汀2.275 mg/（kg·d）灌胃8周,模型对照组、正常组予等量生理盐水灌胃。HE染色观察小鼠动脉粥样硬化斑块形成情况,全自动生化分析仪检测血脂水平,Western blot检测主动脉ULK1、Beclin1、LC3、p-mTOR的蛋白表达。结果 与正常组相比,模型对照组TG、TC和LDLC水平升高（P〈0.05）,HDLC水平降低（P〈0.05）,主动脉管腔见较大粥样斑块,ULK1、Beclin1、LC3蛋白表达水平下调（P〈0.01）,pmTOR蛋白表达水平上调（P〈0.01）;与模型对照组相比,绞股蓝总甙组和辛伐他汀组TG、TC和LDLC水平降低（P〈0.05）,HDLC水平升高（P〈0.05）,主动脉管腔粥样斑块明显减少,ULK1、Beclin1、LC3蛋白表达水平上调（P〈0.01）,p-mTOR蛋白表达水平呈下调趋势（P〈0.01或P〈0.05）。结论 绞股蓝总甙可能通过调控自噬缓解动脉粥样硬化斑块形成,进而防治动脉粥样硬化。
Aim Based on the mTOR/ULK1 autophagy signaling pathway to discuss the mechanism of gypenoside improving aorta lipid deposition of ApoE-/- mice. Methods 30 healthy ApoE-/- mice were randomly divid- ed into the model control group and the gypenoside group, and the simvastatin group, 10 mice in each group. 10 C57bL/ 6J mice were used as the normal control group. The model control group, the gypenoside group and the simvastatin group were fed with high-fat diet for 4 weeks. The gypenoside group and simvastatin group were treated with gypenoside 2.973 g/（kg·d） and simvastatin 2.275 mg/（kg ·d） by gastrogavage for 8 weeks, respectively. The normal control group and the model control group were given by gastrogavage with the normal saline of the same volume. The formation of atherosclerotic plaque of the mice was detected by HE staining, and the blood lipid level was detected by the fully automatic biochemical analyser. The expressions of ULK1, Beclinl, LC3 and p-mTOR proteins were dectected by the Western blot.Results Compared with normal control group, in the model control group, TG, TC and LDLC were significantly increased （P〈0.05）, HDLC was significantly decreased （P〈0.05）, large atheromatous plaques could be seen in aortic canal, ULK1, Beclinl and LC3 were significantly decreased （P〈0.01） , p-roTOR was significantly increased （P〈0.01）. Compared with the model control group, in the gypenoside group and the simvastatin group, TG, TC and LDLC were signifi- cantly decreased （P〈0.05）, HDLC was significantly increased （P〈0.05）, atheromatous plaques in aortic canal were sig- nificantly decreased, ULK1, Beelinl and LC3 were significantly increased （P〈0.01） , p-roTOR was significantly decreased （P〈0.01 or P〈0.05）. Conclusion Gypenosides could relieve the formation of atheroselerotic plaques and prevent atherosclerosis possibly through regulating the autophagy.
出处
《中国动脉硬化杂志》
CAS
2018年第2期127-132,共6页
Chinese Journal of Arteriosclerosis
基金
辽宁省教育厅一般项目(L201613)
第60批中国博士后科学基金面上资助项目(2016M601331)
国家自然科学基金青年基金项目(81300229)
