局部转染整合素相关激酶改善心肌梗死后大鼠的心功能

The Protective Effect of Integrin Linked Kinase on Cardiac Function in Rats with Experiment Myocardial Infarction Rat

背景整合素相关激酶(ILK)是心肌机械牵拉的一种感受器,对心肌收缩起调节作用。目的探讨心肌局部转染ILK基因对心肌梗死后大鼠的心功能的影响。方法大鼠冠状动脉左前降支结扎制成急性心肌梗死模型,在梗死周围区分别注射表达ILK的腺病毒载体(治疗组,n=8)或者不表达ILK的腺病毒载体(对照组,n=8)。免疫蛋白印迹法测定注射病毒载体后的心肌组织ILK的表达水平。术后4周,心导管法测定大鼠心功能。HE染色和免疫组化染色了解新生血管密度,心脏胶原含量等心肌组织形态变化。结果注射病毒载体后心肌ILK表达水平在2周左右达到顶峰,在4周左右逐渐减低。治疗组大鼠左室压力上升最大速度(+dp/dtmax)[(4930.1±1074.8)mmHg/s]较对照组明显增加[(3325.2±775.9)mmHg/s,P<0.01];治疗组的梗死边缘带的血管密度[(107.6±13.2)/高倍镜视野]较对照组明显增加[(69.0±11.0)/高倍镜视野,P<0.01];治疗组的梗死边缘带组织胶原含量[(27.2±6.3)%]较对照组明显降低[(35.1±9.1)%,P<0.01];治疗组的梗死边缘带的心肌细胞的密度[(320.5±61.6)/高倍镜视野]明显高于对照组[(280.9±58.9)/高倍镜视野,P<0.01],而治疗组的梗死边缘带的心肌细胞横径[(17.5±2.9)μm]要低于对照组[(24.1±3.6)μm,P<0.01]。结论梗死局部心肌的ILK局部注射,加强基因表达,可以改善梗死后大鼠的心功能,这可能和改善梗死周围区的血管生成和胶原含量,从而减轻组织缺血有关。

Background Integrin linked kinase is a new component of the cardiac mechanical stretch sensor, modulating myoeardiae contractility. Objective To test the hypothesis that enhanced level of ILK expression might protect cardiac function in rats with experiment myocardial infarction. Methods Acute myocardial infarction model was established by left anterior decending coronary artery ligation and were treated with local injection of adenoviral vector expressing ILK（n=8） or placebo （n=8） around the area with myocardial infarction. ILK expression was determined by Western blot. Four weeks after surgery, myocardial function was analyzed by catheterization. Myocardial histology was analyzed by hematoxylin-eosin staining and immunohistochemistry staining. Results Local injection of ILK resulted in increases in expression of ILK reaching a peak level around 2 weeks, and decrease 4 weeks later. Compared with control rats, the rats with ILK transfection had higher ＋dp/dtmax[（4930.1±1074.8） mmHg/s vs （3325.2± 775.9） mmHg/s, P〈0.01], higher vascular density [ （ 107.6 ± 13.2）/400 × field vs （69.0 ± 11.0）/400 × field, P〈 0. 01 ] and lower collagen around myocardial infarction borderline[（27.2±6.3）% vs （35.1±9.1）%, P〈0.01]; as well as higher cellular density [（320.5±61.6）/ 400× field vs （280.9±58.9）/400× field, P〈0.01]. Cardiac myocytes around around the myocardial infarction borderline in the ILK transfection rats were decreased[（17.5 ± 2.9） μm vs （24.1 ± 3.6） μm, P〈0.01]. Conclusion ILK improves cardiac function in experiment myocardial infarction rat, which might be related with the effect on angiogenesis, collagen sythesis, leading to amelioration of myocardiac ischemia of cardiac myocytes.