肾上腺髓质素、内皮素-1对大鼠肢体缺血再灌注致心肌损伤的影响

Effect of adrenomedullin,endothelin-1 on myocardial injury after hind limbs ischemia reperfusion in rats

目的观察大鼠肢体缺血再灌注(LIR)后肾上腺髓质素(ADM)与内皮素-1(ET-1)的变化,探讨ADM/ET-1的平衡在LIR致心肌损伤中的作用。方法在大鼠LIR损伤模型上,应用受体阻断剂进行干预,将Wistar大鼠随机分成对照组(Control组)、肢体缺血再灌注组(LIR组)、CGRP8-37+LIR组(CGRP8-37组)和BQ123+LIR组(BQ123组)。采用放射免疫方法测定血浆和心肌组织ADM、ET-1含量的变化;比色法测定血浆活性氧(ROS),心肌组织丙二醛(MDA)、超氧化物歧化酶(SOD)、黄嘌呤氧化酶(XOD)、谷胱甘肽过氧化物酶(GSH-PX)含量的变化;心肌酶学检测。结果大鼠LIR后,血浆和心肌组织ADM、ET-1含量较对照组均明显升高,ADM/ET-1降低(P<0.05),血浆ROS、心肌组织MDA、XOD含量明显升高,SOD、GSH-PX含量降低(P<0.05);心肌酶升高。CGRP8-37组,血浆和心肌组织ADM/ET-1较LIR组进一步降低,心肌损伤加重。BQ123组,血浆和心肌组织ADM/ET-1较LIR组升高,心肌损伤减轻。结论 ADM、ET-1增高可能是大鼠LIR后代偿性自身保护机制之一,ADM/ET-1的失衡参与了LIR后心肌损伤的病理生理过程。

【Objective】To observe the change of drenomedullin（ADM） and endothelin-1（ET-1） after limb ischemia reperfusion（LIR） in rats and to investigate the effect of ADM/ET-1 balance on myocardial in-jury.【Method】On a model of the LIR of rats,we used receptor antagonist to observe the changes.Wistar rats were randomly divided into four groups： control group,LIR group,CGRP8-37（ADM receptor antagonist） ＋ LIR group and BQ123（ET-1 receptor antagonist） ＋ LIR group.The plasma and myocardial tissue contents of ADM and ET-1 were measured by using radioimmunoassay.The biochemical methods were used to mea-sure the contents of reactive oxygen species（ROS）,creatine kinase（CK）,creatine kinase MB isoenzyme（CK-MB） in plasma.The levels of malondialdehyde（MDA）,xanthine oxidate（XOD）,superoxide dismutase（SOD）,glutathione peroxidase（GSH-PX） of myocardium were also observed respectively.【Results】Compared with control group,the contents of ADM,ET-1 in LIR group in plasma and myocardial tissue increased,the ratio of ADM/ET-1 decreased（P 0.05）.The levels of ROS,CK,CK-MB in plasma and MDA,XOD of myocardial tissue were increased,and the content of SOD,GSH-PX were decreased in LIR group（P 0.05）.After using CGRP8-37,the ratio of ADM/ET-1 decreased,the myocardial injury became more serious.Whereas after us-ing BQ123,the ratio of ADM/ET-1 increased,the myocardial injury lightened.【Conclusion】Maybe it was one of the self-protective mechanismas that the content of ADM,ET-1 increased.The unbalance between ADM and ET-1 was involved in the process of athophysidogy of myocardial injury after hind limbs ischemia reperfusion in rats.