肾上腺髓质素对肢体缺血再灌注大鼠心肌损伤的影响

Effect of adrenomedullin on myocardial injury following limb ischemia reperfusion in rats

目的:探讨外源性肾上腺髓质素(ADM)对大鼠肢体缺血再灌注(LIR)后心肌损伤的防治作用及其机制。方法:30只Wistar大鼠随机分为对照组(Control组)、肢体缺血再灌注组(LIR组)和ADM+LIR组(ADM组),每组10只。采用放射免疫方法测定大鼠血浆和心肌组织中内皮素-1(ET-1)含量的变化;比色法测定心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)、黄嘌呤氧化酶(XOD)含量的变化;检测心肌酶学的改变;观察心肌病理学改变;免疫组织化学法检测心肌组织中ET-1的表达。结果:大鼠LIR后,血浆肌酸激酶(CK)、肌酸激酶同工酶(CK-MB)及ET-1含量较对照组均明显升高(P<0.01),心肌组织ET-1、MDA和XOD含量明显升高(P<0.01),SOD含量降低(P<0.01);ADM注入后,血浆CK、CK-MB及ET-1含量降低(P<0.05或P<0.01),心肌组织ET-1、MDA和XOD含量降低(P<0.01),SOD含量升高(P<0.05)。心肌病理学观察显示,LIR组心肌纤维连续性中断呈波浪样改变,形状紊乱,小血管充血明显,内有大量红细胞聚集;ADM注入后心肌损伤明显减轻。心肌组织ET-1免疫组织化学结果显示,LIR组心肌胞浆棕黄色颗粒增多,表达上调;ADM注入后心肌胞浆棕黄色颗粒明显减少(P<0.01)。结论:ADM可能通过抗氧化反应及抑制ET-1的合成对LIR后心肌损伤发挥防治作用。

Objective To observe the protective effect of adrenomedullin（ADM） on the myocardial injury following limb ischemia reperfusion（LIR） in rats and its mechanism.Methods 30 Wistar rats were randomly divided into control group,LIR group and ADM＋LIR group（n=10）.The plasma and myocardial tissue concentrations of endothelin-1（ET-1） were determined by using radioimmunoassay.The levels of creatine kinase（CK）,creatine kinase MB isoenzyme（CK-MB） in plasma and malondialdehyde（MDA）,xanthine oxidate（XOD）,superoxide dismutase（SOD） in myocardial tissue were measured in each group.The pathological changes in the myocardium were observed.Immunohistochemistry technique was used to determine the expression of ET-1 in myocardium.Results Compared with control group,the levels of ET-1,CK,CK-MB in plasma and ET-1,MDA,XOD myocardial tissue were increased（P〈0.01）,and the content of SOD in LIR group was decreased（P〈0.01）.Compared with LIR group,the levels of ET-1,CK,CK-MB in plasma and ET-1,MDA,XOD of myocardial tissue in ADM＋LIR group were decreased（P〈0.05 or P〈0.01）,and the content of SOD was increased（P〈0.05）.The pathological results showed that the myocytes was irregular,the muscle fiber was dissolved,the myofilament was disorder,the marked vascular congestion was observed in LIR group.In ADM＋LIR group,the myocardial injury was lightened.The immunohistochemical results showed that the expression of ET-1 was significantly decreased in ADM group compared with LIR group（P〈0.01）.Conclusion ADM can protect the myocardium following LIR in rats and the protective effects may be related to anti-oxidation and inhibition of synthesis of ET-1.