PPARα信号通路在阿托伐他汀抑制衰老心肌MMP-9表达中的作用

The effect of PPARα signal channel on atorvastatin inhibiting MMP-9 expression in aging myocytes

目的:通过离体实验的方法,观察阿托伐他汀抑制老年大鼠心肌基质金属蛋白酶-9(MMP-9)表达的作用与过氧化物酶体增殖物激活型受体α(PPARα)信号通路之间的关系。方法:分离培养24个月龄大鼠的心肌细胞,将培养的老年大鼠心肌细胞分为四个组,分别为空白对照组、溶剂对照组、阿托伐他汀组、PPARα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(DMSO)、阿托伐他汀、阿托伐他汀+GW6471处理。用RT-PCR方法检测各组大鼠心肌细胞的MMP-9 mRNA表达水平,用Western blot方法检测各组大鼠心肌细胞的MMP-9蛋白含量。结果:①与空白对照组相比,溶剂对照组大鼠心肌细胞的MMP-9 mRNA表达水平和蛋白含量均无显著差异;②与空白对照组相比,阿托伐他汀组的MMP-9 mRNA表达水平和蛋白含量均显著降低(P<0.01);③GW6471+阿托伐他汀组的MMP-9 mRNA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:阿托伐他汀抑制老年大鼠心肌细胞炎性因子MMP-9表达的作用可能与其激活PPARα信号通路有关。

Objective： To investigate the correlation between atorvastatin inhibiting the expression level of matrix metallproteinase 9 （MMP-9） and peroxisomeproliferator activated receptor α（PPARα） signal channel in myocyte of aging rat. Methods： Primary cultures of my ocyte were got ten from aging rats. Myocyte were divided into control group, DMSO group, atorvastatin group, atorvastatin plus GW6471 group, which treated respectively by cell culture medium, DMSO, atorvastatin, atorvastin plus GW6471. The expression of MMP-9 mRNA was evalulated by RT-PCR, and content of MMP-9 protein was detected by Western blot. Results： ①There was no difference between control group and DMSO group in level of MMP-9 mRNA and protein expression （ P 〉 0.05） ; ②The level of MMP-9 mRNA and MMP-9 protein expression in atorvastatin group were significantly lower than those in control group（ P 〈 0.01 ） ; ③Both level of MMP-9 mRNA and protein expression in atorvastatin plus GW6471 group were significantly higher than those in atorvastatin group（ P 〈 0.05）, but were still lower than those in control group（ P 〈 0.05）. Conclusion： Atorvastatin inhibit MMP-9 expression of aging myocytes by PPARα signal channel.