心肌梗死大鼠心室组织Smads蛋白表达及卡托普利的干预作用

目的]研究心肌梗死（myocardial infarction,MI）大鼠心室组织不同区域中Smads蛋白的表达水平及血管紧张素转化酶抑制剂（angiotensin coveroting enzyme inhibitor,ACE I）对Smads表达的影响。方法]采用大鼠心肌梗死模型,随机分为卡托普利（captopril,Cap）组、MI对照组（分为14 d和21 d两组）和假手术组（sham）。对大鼠梗死区、室间隔和右心室中Smad蛋白的表达水平行免疫组化分析。结果]4组大鼠梗死区Smad2/3和Smad4的表达以Cap组最低,21 dMI对照组最高,Smad7的表达呈现Cap组最低而14 dMI对照组最高的趋势;非梗死区Smad2/3和Smad4的表达Cap组最低,MI对照组最高,而Smad7的表达Cap组最低,14 dMI对照组最高;与14 dMI对照组比较,21 dMI对照组Smad2/3、Smad4在梗死区和非梗死区的表达均增高,而Smad7在两个区域的表达均降低（P〈0.05）。结论]MI后早期,R-Smads和Co-Smads表达增高能够促进梗死区的修复,但持续增高最终会导致心肌纤维化。ACEI减轻梗死后心肌纤维化的作用在一定程度上与Smad2/3和Smad4的下调有关。

Effect of angiotensin converting enzyme inhibitor (captopril) on smads protein expression in the infarcted rat heart

Objective] To investigate Smads proteins expression in different regions of cardiac tissue after myocardial infarction, and the effect of captopril on their expression. Methods] Rat model of myocardial infarction （MI） was induced by left coronary artery ligation. Surviving rats were randomly divided into following groups： captopril （2 g/L in drinking water ad libitum）, oper- ation control （ 14 day after MI and 21 day after MI） and sham operation. On day 14 after operation rats were sacrificed and half of the control were killed on day 21. Hearts were removed and prepared for histological analysis and Smad2/3, Smad4 and Smad7 were determined by immunohistochemical method. Results] Smad2/3 and Smad4 protein expression of infracted zone were lowest in Cap group （P 〈 0.05）. The expression of Smad2/3 and Smad4 protein were highest in control group （21 day after MI）, and Smad7 expression was highest in control group （14 day after MI） （P 〈 0.05）. Every Smads protein expression in non-infarcted zone and infarcted zone were at the same level. Compared with control group （ 14 day after MI）, Smad2/3 and Smad4 protein expression of infarcted and non-infarcted zone were all elevated in control group （21 day after MI）, but protein expression of Smad7 were greatly decreased in both zones （P 〈 0.05）. Conclusions] At the early stage after MI, increased expression of R-Smads and Co-Smads are capable to promote tissue repair in the infarcted zone. However, the persistent increment of R-Smads expression eventually induceds myocardial fibrosis. ACEI could alleviate myocardial fibrosis after MI, and the effect is partly via down-regulation of Smad2/3 and Smad4.