血管紧张素转换酶抑制剂对梗死心肌组织钙蛋白酶的影响

Effect of ACE inhibitor on calpain system in infarcted myocardium in rats

目的探讨血管紧张素转换酶抑制剂(ACEI)对梗死心肌组织钙蛋白酶(calpain)系统的调节作用。方法结扎大鼠左冠状动脉复制心肌梗死模型,术前7d起用ACEI雷米普利(rampril)(1mg·kg-1·d-1)。术后1、3、7、14d分别检测左心室游离壁(LVFW)、室间隔(IS)、右室壁(RV)calpainⅠ、Ⅱ及钙蛋白酶抑制剂(calpastatin)蛋白表达。结果室间隔calpainⅠ蛋白表达于心肌梗死14d增加;左室游离壁calpainⅡ蛋白表达于心肌梗死3d达高峰。雷米普利可抑制心肌组织calpainⅠ和Ⅱ的上调,减少心梗面积和间质纤维化,calpastatin蛋白表达不受ACEI的影响。结论CalpainⅠ参与梗死心肌组织的晚期重塑,calpainⅡ参与缺血心肌组织的早期损伤作用。心肌梗死病理过程中,ACEI的心脏保护作用可能与其抑制calpainⅠ、Ⅱ有关。

AIM: To investigate the contribution of angiotensin-converting enzyme inhibitor (ACEI) to the regulation of calpain system in infarcted myocardium. METHODS: Rat myocardial infarction (MI) model was established by permanent ligation of the left coronary artery. The treatment with the ACEI inhibitor rampril (1 mg·kg^-1 ·d^-1 ) was started 7 days prior to surgery. On day 1, 3, 7 and 14 after MI, protein levels of calpainⅠ, Ⅱ and calpastatin were determined in left ventricular free wall (LVFW), interventricular septum (IS) and right ventricule. RESULTS: CalpainⅠprotein level was increased in IS 14 d post MI, whereas the protein level of calpainⅡ was maximally increased in LVFW 3 d post MI. Rampril decreased protein up-regulation of calpainⅠ and Ⅱ, and reduced infarct size and interstitial fibrosis. Calpastatin protein expression was not affected by ACEI. CONCLUSIONS: CalpainⅠ is involved in cardiac remodelling in the late and calpainⅡ contributes to cardiac tissue damage in the early phase of MI. The heart protective effect of ACEI may be related to the inhibition of calpain system in the pathogenesis of myocardial infarction.