瑞舒伐他汀对ApoE^(-/-)小鼠心肌SIRT1信号通路的影响

Effect of Rosuvastatin on the expressions of SIRT1 signal pathw ay in the ApoE^(-/-) mice cardiac myocytes

目的探讨SIRT1、p-FOXO3a信号通路在高脂饮食下ApoE-/-小鼠心脏氧化应激损伤中的保护作用,及瑞舒伐他汀对该通路的影响。方法随机选取C57BL/6J小鼠(对照组)10只,给予普通饮食。选取同品系ApoE-/-小鼠20只,随机分为模型组和干预组,每组10只,均给予高脂喂养。干预组瑞舒伐他汀悬液灌胃,模型组等量生理盐水灌胃。连续喂养16周后处死所有小鼠,全自动生化仪检测血清血脂,HE染色观察各组小鼠心肌细胞形态变化,Western blotting法检测心肌细胞SIRT1、p-FOXO3a的表达,免疫组化法检测心肌SIRT1蛋白的表达,同时检测心脏组织匀浆中SOD、MDA含量。结果模型组较对照组血清TC、TG、LDL-C明显升高(P<0.05),HDL-C显著降低(P<0.05),心肌细胞粗大、排列紊乱,胶原增多,SIRT1、p-FOXO3a表达减少(P<0.05),组织匀浆中SOD降低,MDA增多(P<0.05)。与模型组相比,干预组小鼠血清TC、TG、LDL-C明显降低(P<0.05),HDL-C明显升高(P<0.05),心肌细胞排列整齐,胶原减少,SIRT1、p-FOXO3a表达增加(P<0.05),组织匀浆中SOD增多,MDA降低。结论高脂饮食下ApoE-/-小鼠心脏易发生氧化应激损伤,瑞舒伐他汀可通过上调SIRT1、p-FOXO3a保护心脏免受氧化应激损伤。

Objective To investigate the effects of Rosuvastatin on the expressions of SIRT1 and p-FOXO3a in the ApoE^-/- mice cardiac myocytes. Methods A total of 10 C57BL/6J mice were randomly selected as the control group, which were given ordinary diet. Another 20 ApoE^-/- mice were randomly divided into the model group （n = 10） and treatment group （n = 10）, which were fed with high lipid diet. The treatment group underwent Rosuvastatin suspension gavage, whereas the model group received the same volume of normal saline for 16 weeks. Serum lipid was detected with full-automatic biochemical instrument. The expressions of SIRT1 and p-FOXO3a were evaluated with Western blotting. The expressions of SIRT1, SOD and MDA were detetced with immunohistochemical method. Results TC, TG, LDL-C and MDA significantly increased in the model group than in the control group, but the levels of HDL-C and SOD were lower in the model group （ P 〈 0.05 ）, and the myocytes were hypertrophic. Meanwhile, the expressions of SIRT1 and p-FOXO3a protein in cardiac myocytes of the model group significantly decreased （ P 〈 0.05 ）.Compared with the model group, the levels of TC, TG, LDL-C and SOD significantly decreased whereas HDL-C and MDA increased in the treatment group （P 〈 0.05 ）. The expressions of SIRT1 and p-FOXO3a protein in cardiac myocytes markedly increased and myocardial cells arranged orderly. Conclusion ApoE^-/- mice fed with high-fat diet are prone to oxidative stress injury in cardiac myocytes, while Rosuvastatin can up-regulate the expressions of SIRT1 and p-FOXO3a, protecting the myocardium from such injury.