阿托伐他汀对ApoE基因敲除小鼠动脉粥样硬化病变中TRPC5表达的影响

目的:观察载脂蛋白E基因敲除(Apo E-/-)小鼠动脉粥样硬化斑块形成过程中血管平滑肌细胞瞬时受体电位通道5(TRPC5)蛋白的表达变化,以及阿托伐他汀药物干预对TRPC5的影响并探讨其作用机制。方法:将40只6周龄雄性Apo E-/-小鼠随机分为模型组和他汀干预组,高脂饲料喂养建立动脉粥样硬化模型。他汀干预组给予阿托伐他汀(20 mg·kg-1·d-1)灌胃,模型组给予等量生理盐水灌胃。20只同龄雄性野生型C57BL/6J小鼠给予普通饲料喂养作为正常对照组。各组小鼠分别喂养至20和30周龄,分别取10只取血并处死。取主动脉根部做石蜡切片行HE染色形态学观察,测量并计算斑块相对面积;免疫组织化学染色检测各组小鼠TRPC5蛋白表达变化。取胸腹段主动脉行实时荧光定量PCR,检测主动脉中TRPC5通道蛋白mRNA的表达水平。结果:与模型组相比,阿托伐他汀干预组的血脂明显下降,斑块总面积明显减小,TRPC5蛋白水平及mRNA含量明显下降;30周龄模型组的TRPC5蛋白表达稍高于20周龄模型组,但差异无统计学意义;30周干预组较20周干预组相比,TRPC5水平有降低趋势且差异有统计学意义。结论:阿托伐他汀可能通过下调TRPC5蛋白表达从而延缓动脉粥样硬化进程。

Effect of atorvastatin on TRPC5 expression in atherosclerosis of apolipoprotein E-knockout mice

AIM: To observe the changes of transient receptor potential channel 5 (TRPC5) in vascular smooth muscle cells (VSMCs) of apolipoprotein E-knockout (ApoE^-/-) mice and the effect of atorvastatin interference, and to investigate the mechanism of atorvastatin therapy. METHODS: Male ApoE^-/- mice at 6 weeks of age were used to establish the atherosclerosis model by feeding with hyperlipidic diet. The mice were randomly divided into model group and atorvastatin group. The mice in atorvastatin group were lavaged with atorvastatin at 20 mg·kg^-1·d^-1, while the mice in model group received normal saline. The healthy C57BL/6J mice with the same age and the same genetic background, feeding with ordinary food, served as control group. At the time points of 14 and 24 weeks, the mice were sacrificed. The serum was collected for detecting the lipid levels. The aortic roots of the heart were taken to make paraffin sections with HE staining for measuring and comparing the relative atherosclerotic plaque area in each section. The expression of TRPC5 in VSMCs was examined with immunohistochemical staining. The mRNA levels of TRPC5 in the serum and the thoracoabdominal aorta were measured by real-time PCR. RESULTS: Compared with model group, blood lipids in atorvastatin group were significantly decreased, and the formation of plaque under aorta intima also decreased. The protein expression of TRPC5 in atorvastatin group decreased significantly compared with model group. Compared with 20-week model group, TRPC5 in 30-week model group showed increasing tendency, but has no statistical significance. Compared with 20-week atorvastatin group, TRPC5 of 30-week atorvastatin group declined. CONCLUSION: Atorvastatin suppresses TRPC5 expression, thus attenuating atherosclerotic development in ApoE^-/- mice.