阿司匹林抑制脂多糖诱导RAW264.7细胞MMP-9表达及机制研究  

Inhibitory effect of aspirin on the expression of MMP-9 and its mechanism in LPS-induced RAW264.7 cells

作　　者：张平[1] 沈陈林 李琳[1] 张炜[1] 姚成增[2] 黄晓晖[1] 

机构地区：[1]安徽医科大学药学院 [2]上海中医药大学附属曙光医院心内科,上海201203

出　　处：《中国临床药理学与治疗学》2015年第4期388-393,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然科学基金项目(81173133)

摘　　要：目的:探讨阿司匹林对脂多糖(LPS)诱导RAW264.7细胞中基质金属蛋白酶-9(matrix metalloproteinase-9,MMP-9)的表达及其机制研究。方法:MTT法检测LPS诱导RAW264.7细胞作用下,阿司匹林对细胞毒性的影响。Q-RT-PCR检测MMP-9 mRNA表达,免疫蛋白印迹法(western blot)检测MMP-9、p38MAPK及磷酸化p38(Phospho-p38,P-p38)蛋白表达。特异性抑制剂SB203580(SB)阻断p38MAPK通路后,分别应用Q-RT-PCR和Western blot检测MMP-9的基因和蛋白表达。结果:阿司匹林呈剂量依赖性抑制MMP-9基因和蛋白表达。与LPS组相比,阿司匹林可明显抑制P-p38MAPK蛋白的表达,而p38MAPK总蛋白无明显变化。抑制p38MAPK通路后,MMP-9 mRNA和蛋白水平均明显下调。结论:阿司匹林抑制LPS诱导RAW264.7细胞中MMP-9表达可能与抑制p38MAPK信号转导通路有关,进而发挥其抗AS药理作用。AIM ： To investigate the effect of as- pirin on the expression of MMP-9 and its mechanism in LPS-induced RAW264. 7 ceils. METHODS： The cytotoxic effect of aspirin on LPS-induced RAW264.7 cells was detected by MTT assay. MMP- 9mRNA expression was detected by quantitative real-time PCR. The protein expression level of MMP-9, p38MAPK and Phospho-p38 （ P-p38 ） were exam- ined by western blotting. After the inhibition of p38MAPK pathway by specific inhibitor SB203580, the gene and protein expression of MMP-9 was meas- ured by Quantitative real-time PCR and western blot-ting separately. RESULTS：The gene and protein expression of MMP-9 were inhibited by aspirin in dose-dependent manner. The protein expression of P- p38 was significantly inhibited by aspirin as com- pared with LPS treatment group. However, the pro- tein expression of p38MAPK was not significantly different. The expression of MMP-9mRNA and pro- tein were p38MAPK obviously decreased after inhibiting pathway. CONCLUSION ： The results suggest that aspirin has potent anti-atherosclerotic action with inhibitory action on MMP-9 production by blocking p38MAPK pathway in LPS-induced RAW264.7 cells.

关 键 词：阿司匹林 基质金属蛋白酶 动脉粥样硬化 巨噬细胞 

分 类 号：R965.2[医药卫生—药理学]