血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白表达及胶原沉积的影响

Angiotensin Ⅱ Type 1 Receptor Blocker Inhibits Osteopontin Expression and Interstitial Fibrosis Infiltration in Rats With Myocardial Infarction

目的:探讨血管紧张素Ⅱ-1型受体拮抗剂对心肌梗死大鼠骨桥蛋白(OPN)的表达及心肌间质胶原沉积的影响。方法:将心肌梗死后24小时存活大鼠随机分为两组:盐水组(16只,5ml/d),厄贝沙坦组[17只,45mg/(kg·d)];另设假手术组(15只)作对照。分别于心肌梗死后4周:导管法测定左心室有创血流动力学及心功能;组织学方法检测非梗死区胶原纤维沉积和心肌细胞横径;Western blot法检测心肌组织骨桥蛋白表达。结果:盐水组与厄贝沙坦组大鼠梗死面积相似,无显著性差异(P>0.05);假手术组大鼠心肌组织Western blot法未检测到骨桥蛋白表达,盐水组大鼠心肌组织有大量骨桥蛋白表达,该上调的蛋白能被厄贝沙坦治疗显著抑制(P<0.01)。与假手术组相比,所有心肌梗死大鼠均出现显著的心肌间质纤维沉积,左心室相对重量增大,非梗死区心肌细胞横径增加,均有显著性差异(P均<0.01);与盐水组相比,厄贝沙坦组心肌间质纤维沉积减轻,左心室相对重量及非梗死区心肌细胞横径降低,均有显著性差异(P均<0.01)。与假手术组相比,所有心肌梗死大鼠在4周后均表现出左心室收缩压和左心室压力最大上升和下降速率显著下降,左心室舒张末压显著上升,均有显著性差异(P均<0.01),提示了显著的左心室收缩和舒张功能不全;与盐水组相比,厄贝沙坦组大鼠心功能显著改善,均有显著性差异(P均<0.01)。结论:心肌梗死后大鼠心肌组织出现大量骨桥蛋白表达,厄贝沙坦治疗显著抑制心肌梗死大鼠骨桥蛋白的表达,并能改善心肌的纤维化,改善心脏功能。

Objective：To elucidate the effects of angiotensin Ⅱ type 1 receptor blocker （irbesartan） on cardiac osteopontin expression and interstitial fibrosis infiltration in myocardial infarcted （MI） rats. Methods：After ligating left anterior descending coronary artery, 33 rats that survived 24 h were randomly divided into two groups：MI-saline group （n = 16,5 ml/d） and MI-irbesartan group （n = 17,45 mg/（ kg·d） ）. Sham operated group （n = 15 ） was selected as noninfarcted control. At 4 weeks after drug therapy by gastric gavage,hemodynamics and left ventricular function were measured with catheterization, interstitial fibrosis infiltration and cardiomyocyte diameter were evaluated with histological methods,and myocardium osteopontin protein expression level was detected with Western blot. Results ：There was no significant difference in infarcted area between the two MI groups（P 〉0.05）. No osteopontin protein was detected in myocardium of sham-operation rats. High level osteopontin protein expression was detected and irbesartan significantly suppressed increased osteopontin protein expression in MI rats at 4 weeks（P 〈0.01 ）. Compared with the sham operated group,rats in MI-saline group and MI-irbesartan group showed marked interstitial fibrosis infiltration in the non-infarction area, higher ventricular weight/body weight ratio, significantly increased cardiomyocyte diameter （ P 〈 0. 01, respectively）, and devel-oped significant systolic and diastolic dysfunction,as was indicated by decreased LVSP and ± dp/dtmax, as well as increased LV- EDP（ P 〈 0. 01,respectively）. Irbesartan significantly prevented cardiac fibrosis and systolic and diastolic dysfunction（P 〈 0. 01, respectively）. Conclusions：Osteopontin protein expression was increased in myocardial infarcted rats. Angiotensin 11 type 1 receptor blocker inhibits osteopontin expression and cardiac fibrosis after MI.