摘要
目的:观察阿托伐他汀下调老年大鼠心肌肿瘤坏死因子-α(TNF-α)表达的作用及其与过氧化物酶体增殖物激活型受体β/δ(PPARβ/δ)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,将心肌细胞分为空白对照组、溶剂对照组、阿托伐他汀组、阿托伐他汀+PPARβ/δ拮抗剂GSK0660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+GSK0660处理。用RT-PCR方法检测各组大鼠衰老心肌细胞的TNF-αmRNA表达水平,用western blot方法检测各组TNF-α蛋白含量。结果:(1)与空白对照组相比,溶剂对照组大鼠衰老心肌细胞的TNF-αmRNA和蛋白水平均无显著差异;(2)与空白对照组相比,阿托伐他汀组的TNF-αmRNA和蛋白水平含量均显著降低(P<0.01);(3)阿托伐他汀+GSK0660组的TNF-αmRNA表达水平及蛋白含量均显著高于阿托伐他汀组,但仍低于空白对照组(P<0.05)。结论:阿托伐他汀可通过激活PPARβ/δ信号通路下调衰老心肌细胞TNF-α的表达。
Objective：To investigate the effects of atorvastatin on tumor necrosis factor-α （TNF-α） expression in aging cardiomyoeytes and the role of peroxisome proliferator activated receptor β/δ （PPARβ/δ） signal pathway. Methods：Senescent cardiomyocytes obtained from aging rats of 24 months old were randomly divided into control group, DMSO group, atorvastatin group and atorvastatin ＋ GSK0660 group, which were treated by cell culture medium, DMSO, atorvastatin, atorvastatin ＋ GSK0660, respectively. The mRNA levels of TNF-α were evaluated by RT-PCR, and the protein contents of TNF-α were detected by western blot. Results：（ 1 ） There were no differences in the mRNA and protein levels of TNF-α between control group and DMSO group （P〉0.05） ; （2） The mRNA and protein levels of TNF-α in atorvastatin group were significantly lower than those in control group （P〈0.01 ） ; （3） Both mRNA and protein expression of TNF-α in atorvastatin ＋ GSK0660 group were higher than those in atorvastatin group （P〈0.05 or P〈0.01）, but were lower than those in control group （P 〈0.05）. Conclusion： Atorvastatin can down-regulate TNF-α expression in senescent cardiomyocytes by activating PPARβ/δ signal pathway.
出处
《国际心血管病杂志》
2014年第2期120-123,共4页
International Journal of Cardiovascular Disease
基金
国家自然科学基金资助项目(70872713)
