厄贝沙坦联合缺血后适应对糖尿病大鼠缺血再灌注损伤早期心肌纤维化及心室重构的影响

Effects of Irbesartan to Early Myocardial Fibrosis and Ventricular Remodeling on Diabetic Rats After Ischemia Reperfusion Injury

目的探讨厄贝沙坦联合缺血后适应对2型糖尿病大鼠缺血再灌注损伤早期心肌纤维化及心室重构的影响及机制。方法选取SD大鼠40只,建立2型糖尿病大鼠模型,随机分为4组(n=10):1假手术组;2缺血再灌注对照组(对照组);3缺血后适应组(Post组);4厄贝沙坦后处理+缺血后适应组(Eba+Post组)。检测各组大鼠血清肌钙蛋白c Tn T以及心肌酶CK-MB、血清AT1受体自身抗体及心肌AT1R m RNA的表达;HE染色和电镜测定大鼠心肌间质纤维化及心肌炎性水平,以及各组大鼠心重指数和心肌胶原蛋白含量。结果 Post组CK-MB和c Tn T水平均低于对照组(均P<0.05),Eba+Post组CK-MB和c Tn T水平低于Post组,P<0.05;Post组及Eba+Post组抗AT1R受体阳性率分别为30%(3/10)和20%(2/10),明显低于对照组50%(5/10),P<0.05;Post组、Eba+Post组大鼠治疗后AT1R m RNA的表达明显减少,均明显低于对照组,P<0.05,与Post组相比,Eba+Post组AT1R m RNA的表达显著减少,P<0.05;HE染色切片及电镜检查显示,Post组、Eba+Post组心肌超微结构的改善明显,Eba+Post组心肌炎症及心肌纤维化的改善效果更为明显;对照组、Post组及Eba+Post组心重指数及心肌胶原蛋白含量较假手术组升高,治疗组上述指标均显著下降,Eba+Post组心重指数及心肌胶原蛋白含量较Post组降低,P<0.05。结论在高血糖大鼠心肌缺血再灌注条件下,ARB药物后处理对心肌缺血后适应有协同保护作用,其机制可能与调节AngⅡ、AT1R的水平有关,可改善早期心肌纤维化,减轻早期心室重构。

Objective To investigate the effects of irbesartan to early myocardial fibrosis and the effect of ventricular remodeling on diabetic rats after ischemia reperfusion injury. Methods 40 SD type 2 diabetic rats models were established, and randomly divided into 4groups（n = 10）： 1sham group; 2ischemia reperfusion group（control group）; 3ischemic postconditioning group（Post group）; 4irbesartan post-processing ＋ ischemic postconditioning group（Eba ＋ Post group）. Serum troponin c Tn T and the level of myocardial enzyme CK-MB,serum AT1 receptor autoantibodies and myocardial AT1 R m RNA expression, myocardial interstitial fibrosis and inflammation levels, heart /heavy index and myocardial collagen content were detected. Results In Post group, CK-MB and c Tn T levels were lower than the control group（P〈0.01）, in the Eba ＋ Post group, CK-MB and c Tn T levels were lower than the post group, P〈0.05; in Post group and Eba ＋ Post group, the positive rate of AT1 resistance R receptor was 30%（3/10） and 20%（2/10） respectively, significantly lower than 50%（5/10） of control group, P〈0.05; AT1 R m RNA expression decreased significantly in Post group and Eba ＋ Post group, which were significantly lower than the control group, P〈0.05, compared with Post group, AT1 R m RNA expression was significantly lower in Eba ＋ Post group, P〈0.05;HE staining slices and electron microscopic examination showed that the improvement of the myocardial ultrastructure was obviously in Post group and Eba ＋ Post group. Compared with Post group, myocardial inflammation and myocardial fibrosis effect were improved more obviously in Eba ＋ Post group. Compared with the Post group and Eba ＋ Post group, heart / heavy index and myocardial collagen content were higher in the control group. Conclusions ARB drugs postprocessing has coordinated protection on ischemic postconditioning after myocardial ischemia. The mechanism may be related to regulating of AngⅡ, and the level of the AT1 R. So it can improve early myocardial fibrosis and reduce early ventricular remodeling.