阿托伐他汀通过PPARα信号通路抑制老年大鼠心肌TNF-α的表达

Inhibited TNF-α Expression of Atorvastatin in Aged Rats Involving PPARα Signal Pathway

目的观察阻断过氧化物酶体增殖物激活物受体α(PPARα)信号通路对阿托伐他汀抑制老年大鼠心肌肿瘤坏死因子-α(TNF-α)表达作用的影响。方法分离培养24个月龄大鼠的心肌细胞,将培养的细胞分为空白对照组、溶剂对照组、阿托伐他汀组、PPAR拮抗剂GW6471+阿托伐他汀组。各组细胞分别加入细胞培养液、二甲基亚砜、阿托伐他汀、阿托伐他汀+GW6471处理。分别用RT-PCR和Western blot方法检测各组大鼠心肌细胞的TNF-αmRNA表达水平和蛋白含量。结果 (1)与空白对照组相比,溶剂对照组细胞的TNF-αmRNA表达水平和蛋白含量均无显著差异(P>0.05);(2)与空白对照组相比,阿托伐他汀组的TNF-αmRNA表达水平和蛋白含量均显著降低(P<0.01);(3)GW6471+阿托伐他汀组的TNF-αmRNA表达水平及蛋白含量均显著高于阿托伐他汀组(P<0.05),但仍低于空白对照组(P<0.05)。结论阿托伐他汀可通过激活PPARα信号通路来抑制老年大鼠心肌细胞炎性因子TNF-α表达。

Objective To investigate the inhibited TNF-α expression of atorvastatin involving PPARα signal pathway in myocytes of aged rats. Methods Primary cultures of myocytes were from aged rats. Myocytes were divided into 4 groups：control group, DMSO group ,atorvastatin group,atorvastatin plus GW6471 group, treated with culture medium of cardiac myocytes ,DMSO, atorvastatin, atorvastin plus GW6471 group,respectively. The expression of TNF-α mRNA and protein was measured by RT-PCR and Western blot. Results （ 1 ） There was no difference between control group and DM- SO group in the expression level of TNF-ct mRNA and protein（ P 〉0.05） ;（2）The expression level of TNF-α mRNA and TNF-α protein in atorvastatin group was more significantly inhibited than that of control group（ P 〈 0.01 ） ;（3）The mRNA and protein expression level of TNF-α in atorvastatin plus GW6471 group was significantly higher than that of atorvastatin group（ P 〈0.05 ）, but lower than that of control group （ P 〈 0.05）. Conclusion Atorvastatin inhibits the TNF-α expression in cardiac myocytes of aged rats through PPARα signal pathway.