大鼠心肌梗死后心肌NF-κB、MMP-2和TIMP-2表达变化及其意义

Expression of NF-κB, metalloproteinases and tissue inhibitor of metalloproteinases in rat ventricular remodeling after acute myocardial infarction

目的探讨心肌梗死(MI)后大鼠心肌NFκB、MMP2和TIMP2表达变化及其在心室重构和心力衰竭的病理意义。方法结扎冠状动脉左前降支复制大鼠心肌梗死模型。术后24h将存活大鼠随机分为MI组及假手术(SH)组。采用免疫组化法及免疫印迹法观察MMP2和TIMP2在MI后不同时间点的表达变化,采用凝胶电泳迁移率变化法分析NFκB活性变化。结果MI后NFκB活性明显增强,在心肌细胞中表达呈阳性。MI后心肌MMP2、TIMP2表达均增加。从时间的相关性看,MI后时间越长,心功能越差,MMP2相对含量越高,而TIMP2表达则随梗死时间延长而减弱。结论大鼠MI后心肌组织中NFκB活性和MMP2、TIMP2表达水平都发生了明显变化,可能参与了MI后心室重构的病理过程。

AIM To observe changes of expression of NF-κB, metalloproteinase-2 （MMP-2） and tissue inhibitor of metalloproteinases-2 （ TIMP-2 ） during ventricular remodeling following acute myocardial infarction and to investigate its pathological significance. METHODS The myocardial infarction model was established on rats by ligation of coronary artery. Twenty four hours after the operation, rats were randomly divided into operation group and sham group. The protein expressions of MMP-2 and TIMP-2 were examined by immunohistochemical analysis and Western-blot. The change of NF-κB activity was analyzed by EMSA. RESULTS The activity of NF-κB was enhanced after myocardial infarction and the expressions of MMP-2 and TIMP-2 were elevated （P 〈 0 . 0 5 ） . CONCLUSION NF-KB activity and expressions of MMP-2 and TIMP-2 change significantly after myocardial infarction, suggesting that all the three factors maybe involved in ventricular remodeling following acute myocardial infarction.