阻断PPARβ/δ途径对阿托伐他汀抑制衰老心肌细胞中MMP-9表达的影响  

Effect of blocking PPARβ/δ signal channel on atorvastatin in inhibiting MMP-9 expression in aging cardiomyocytes

作　　者：韩磊 叶平[2] 李鸣皋 

机构地区：[1]解放军海军总医院全军航海航空医学中心,北京100048 [2]解放军总医院老年心血管二科,北京100853

出　　处：《心脏杂志》2013年第6期633-636,共4页Chinese Heart Journal

基　　金：国家自然科学基金项目资助(70872713)

摘　　要：目的:观察阻断过氧化物酶增殖物激活型受体β/δ(peroxisome proliferator activated receptorβ/δ,PPARβ/δ)信号通路对阿托伐他汀抑制老年大鼠心肌细胞基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)表达的影响。方法:分离培养24个月龄大鼠的心肌细胞,将培养的心肌细胞分为空白对照组、溶剂对照组、阿托伐他汀组及PPARβ/δ拮抗剂GSK0660+阿托伐他汀组,4组细胞依次分别加入细胞培养液、二甲基亚砜(dimethyl sulfoxide,DMSO)、阿托伐他汀及阿托伐他汀+GSK0660处理。用RT-PCR方法检测各组大鼠心肌细胞中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蛋白的含量。结果:①与空白对照组相比,溶剂对照组大鼠心肌细胞中MMP-9 mRNA表达水平和其蛋白含量均无显著差异,阿托伐他汀组心肌细胞中MMP-9 mRNA表达水平和其蛋白含量均显著降低(P<0.01);②GSK0660+阿托伐他汀组心肌细胞中MMP-9 mRNA表达水平及其蛋白含量均显著高于阿托伐他汀组(P<0.05或P<0.01),但仍低于空白对照组(P<0.05)。结论:阿托伐他汀可激活PPARβ/δ信号通路下调衰老心肌细胞中MMP-9的表达。AIM：To investigate the effect of blocking peroxisome proliferator activated receptor β/δ （PPARβ/δ） signal channel on the action of atorvastatin in inhibiting matrix metalloproteinase9 （MMP-9） expression in cardiomyocytes of aging rats. METHODS： Primary cardiomyocytes were cultured in aging rats. Cardiomyocytes were divided into control group, dimethyl sulfoxide （DMSO） group, atorvastatin group and atorvastatin plus GSK0660 group, which were treated by cell culture medium, DMSO, atorvastatin, and atorvastin plus GSK0660, respectively. Expression of MMP-9 mRNA was evaluated by RTPCR and the content of MMP-9 protein was detected by Western blot. RESULTS： No difference was observed in the expression level of MMP-9 mRNA and protein between control group and DMSO group. Expression level of MMP-9 mRNA and MMP-9 protein in atorvastatin group was significantly lower than in control group （P〈0.01）. Both mRNA and protein expression levels of MMP-9 in atorvastatin plus GSK0660 group were higher than in atorvastatin group （P〈0.05 or P〈0.01） but still lower than those in control group （P〈0.05）. CONCLUSIONS： Atorvastatin downregulates the expression of MMP-9 in aging cardiomyocytes by activating PPARβ/δ signal channel.

关 键 词：阿托伐他汀 过氧化物酶增殖物激活型受体β δ 基质金属蛋白酶-9 心肌细胞 衰老大鼠 

分 类 号：R972.6[医药卫生—药品]