2型糖尿病大鼠心肌血红素氧合酶-1表达水平与氧化应激水平的关系

摘要

目的 探讨2型糖尿病大鼠心肌血红素氧合酶-1(HO-1)不同表达水平与心肌氧化应激水平的关系.方法 健康SD大鼠64只随机分为8组:空白6周(NC1)组、糖尿病6周(DM1)组、糖尿病加血红素6周(HE1)组、糖尿病加原卟啉锌(ZnPP)6周(ZN1)组;空白9周(NC2)组、糖尿病9周(DM2)组、糖尿病加血红素9周(HE2)组、糖尿病加原卟啉锌9周(ZN2)组,每组8只;分别在第6、9周处死大鼠,免疫组织化学法检测心肌HO-1表达水平,比色法检测心肌氧化应激水平,电子显微镜显示心脏超微结构改变.结果 (1) HE1、HE2组心肌HO-1的表达水平分别高于DM1、DM2组(P<0.05、P<0.05),显著高于NC1、NC2组(P<0.01、P<0.01)和ZN1、ZN2组(P<0.01、P<0.01).(2)ZN1、ZN2心肌HO-1的表达水平低于NC1、NC2组(P<0.05、P<0.05);(3) HE1、HE2心肌纤维化程度和心肌线粒体超微结构损害明显低于DM1、DM2组和ZN1、ZN2组;(4)HE1、HE2组血清SOD和GSH-PX水平高于DM1、DM2组和ZN1、ZN2组(P<0.05,P<0.05;P<0.05,P<0.0 1)和(P<0.05,P<0.05;P<0.01,P<0.01),MDA水平低于DM1、DM2组和ZN1、ZN2组(P<0.01)而与NC1、NC2组比较,差异无统计学意义(P＞0.05).结论 (1)血红素可以提高心肌HO-1表达水平;(2) 提高HO-1表达水平可增强2型糖尿病大鼠心肌抗氧化应激能力,减轻心肌损害.%Objective To explore the relationship of the different level of HO-1 expression and the myocardial oxidative stress of type 2 diabetic rats. Methods 64 healthy SD rats were divided into eight groups randomly;six weeks blank group(NCl) ,six weeks diabetic group(DM1) , six weeks diabetic ＋ heme group ( HE1), six weeks diabetic ＋ ZnPP group (ZN1); nine weeks blank group (NC2),nine weeks diabetic group(DM2) ,nine weeks diabetic+heme group(HK2) , nine weeks diabetic ＋ ZnPP group ( ZN2); each group contains eight rats and these rats would be killed in the sixth and ninth week to measure myocardial HO-1 express by IHCA; detect myocardial oxidative stress level by colorimetric method;display the change of myocardium ultra microstructure by electron microscope. Results (1) the expression level of HO-1 in group HE1,HE2 were higher than group DM1,DM2 respectively(P<0. 05,P<0. 05), and markedly higher than group NCI ,NC2(P<0. 01,P<0. 01) and group ZN1, ZN2 respectively(P<0. 01,P<0. 01). (2)the expression level of HO-1 in group ZN1.ZN2 are lower than group NC1,NC2 respectively(P<0. 05,P<0. 05). (3) the degree of myocardium fibrosis and the ultrastructural damage of myocardium mitochondria in group HE1, HE2 were lighter than group DM1,DM2 and group ZN1,ZN2 respective ly. (4)the level of SOD,and SH-PX in group HE1,HE2 were higher than group DM1,DM2 and group ZNl,ZN2(P<0. 05,P<0. 0 5;P<0. 05,P<0. 01)and(P<0. 05,P<0. 05;P<0. 0 l,P<0. 01),the level of MDA were lower than group DM1,DM2 and group ZN1,ZN2(P<0. 01) respectively but it was no statistical difference with group NCI ,NC2. Conclusion (l)Heme can induce HO-1 express in myocardium. (2)Enhance the level of HO-1 can strengthen Protect Type 2 diabetic rats myocardium against oxidative stress. Thus it can alleviate pathological lesion.