阿司匹林调节小鼠腹腔巨噬细胞MMP-2/9和TIMP-1基因的表达及分泌  

Modulation of Aspirin on Gene Expression and Release of MMP-2/9 and TIMP-1 in Macrophages of Mice

作　　者：姚义琴[1] 谢梅林[1] 薛洁[1] 张克平[1] 朱路佳[1] 

机构地区：[1]苏州大学医学部药理学系,江苏苏州215123

出　　处：《苏州大学学报（医学版）》2009年第3期422-425,共4页Suzhou University Journal of Medical Science

基　　金：江苏省自然科学基金资助项目(BK2005029)

摘　　要：目的研究阿司匹林对小鼠腹腔巨噬细胞基质金属蛋白酶(MMP)-2/9和基质金属蛋白酶组织抑制因子-1(TIMP-1)基因表达及分泌的影响。方法培养的小鼠腹腔巨噬细胞用阿司匹林处理后,用RT-PCR方法检测MMP-2/9和TIMP-1mRNA表达,用ELISA方法测定培养上清液中MMP-2/9和TIMP-1的含量。结果小鼠腹腔巨噬细胞经用阿司匹林12.5～50μg/ml处理24h后,MMP-2/9mRNA表达及分泌至培养上清液中的含量明显降低,MMP-2的降低百分率分别为18.6%～86.8%和37.7%～53.3%,MMP-9的降低百分率分别为32.1%～78.3%和6.5%～14.3%;而TIMP-1mRNA的表达及分泌却显著提高,其增加百分率分别为60.5%～110.9%和94.4%～80.6%。结论阿司匹林可抑制MMP-2/9的基因表达及分泌,同时还可增加TIMP-1的基因表达及分泌,这一效应对增加动脉粥样硬化斑块的稳定性和预防心血管事件的发生具有有利的作用。Objective To investigate whether aspirin affected the MMP-2/9 and TIMP-1 gene expression and release in cultured macrophages of mice. Methods The mRNA expression of MMP-2/9 and TIMP-1 was determined by reverse transcription-polymerase chain reaction, while the protein level of MMP-2/9 and TIMP-1 in cultured cell supernatants was determined by enzyme linked immunosorbent assay after mouse celiac macrophages were treated with aspirin. Results The mRNA expression and protein level of MMP-2/9 was decreased after treatment with aspirin 12.5-50 μg/ml for 24 h, the decreased percentage was 18.6%-86.8%（mRNA expression） and 37.7%-53.3% （protein level） for MMP-2, 32.1%-78.3%（mRNA expression） and 6.5% -14.3% （protein level） for MMP-9, respectively. While the mRNA expression and protein level of TIMP-1 were inversely increased, the increased percentage was 60.5%-110.9%（mRNA expression） and 94.4%-80.6% （protein level）, respectively. Conclusion Aspirin can inhibit the gene expression and release of MMP-2/9, and increase the gene expression and release of TIMP-1, and the effects might be good for the stabilization of atheroselerotic plaques and prevention of cardiovascular events.

关 键 词：阿司匹林 MMP-2 MMP-9 TIMP-1 巨噬细胞 小鼠 

分 类 号：R972[医药卫生—药品]