肺动脉高压大鼠心肌MMP-2,9和TIMP-1表达的变化

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[目的]研究大鼠肺动脉高压后基质金属蛋白酶(MMPs)和金属蛋白酶组织抑制因子(TIMPs)在左右心室中表达与在心室重构中的作用。[方法]60只SD随机等分为5组,每组12只,1个对照组和4个肺动脉高压实验组(PAH组),分别于4个时间点(MCT注射后第1,2,3,4周)取材。将MCT注射后第1,2,3,4周的4个肺动脉高压实验组(PAH组)分别简称PAH1、PAH2、PAH3和PAH4实验组。采用酶谱法、免疫印迹(western Blotting)、逆转录-聚合酶链反应(RT-PCR),探讨基质金属蛋白酶-2,9(MMP-2,9)蛋白和mRNA的变化规律。[结果](1)右心室MMP-2,9 mRNA在肺动脉高压后1周增加达高峰,以后逐渐下降但到4周时比对照组仍然要高,并且差异有统计学意义(P﹤0.01)。TIMP-1 mRNA在肺动脉高压后从第1周就开始减少,一直到第4周仍然减少,与对照级比较,差异有统计学意义(P﹤0.01)。(2)左心室MMP-2,9蛋白水平在大鼠肺动脉高压后活性稍增强,表达稍增加,而TIMP-1蛋白含量也稍减少,与对照组相比没有统计学差异,并不导致左心室重构。[结论]MMP-2,9蛋白活性与表达在大鼠肺动脉高压右心室心肌中增强,而TIMP-1蛋白活性与表达减少,它们可能与右心室心肌重塑有关。左心室并不重构。 [Objective] To investigate the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in left ventricle and right ventricle after pulmonary hypertension in rats and their roles in ventricular remodeling. [Methods] Sixty SD rats were randomly divided into 5 groups, 12 rats in each group, 1 control group and 4 pulmonary hypertension group (PAH group). At 4 time points , 4 weeks) drawn. Four experimental groups of pulmonary hypertension (PAH group) at 1, 2, 3, and 4 weeks after MCT injection were referred to as PAH1, PAH2, PAH3 and PAH4 experimental groups respectively. The changes of protein and mRNA of MMP-2, 9 were investigated by enzyme-linked immunosorbent assay (ELISA), Western Blotting and reverse transcription-polymerase chain reaction (RT-PCR) [Results] (1) The expression of MMP-2 and MMP-9 mRNA in the right ventricle peaked at 1 week after pulmonary hypertension and then decreased gradually but remained higher than that of the control group at 4 weeks (P <0.01) . TIMP-1 mRNA decreased from the first week after pulmonary hypertension, and still decreased till the fourth week. Compared with the control group, the difference was statistically significant (P <0.01). (2) The activity of MMP-2 and MMP-9 in the left ventricle increased slightly after pulmonary hypertension in rats, but slightly increased, while the content of TIMP-1 protein also decreased slightly, which was not statistically different from the control group Ventricular remodeling. [Conclusion] The activity and expression of MMP-2, 9 protein in right ventricular myocardium of pulmonary hypertension rats increased, while the expression and activity of TIMP-1 protein decreased, they may be related to remodeling of right ventricular myocardium. Left ventricle does not reconstruct.
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