氯沙坦对大鼠心肌缺血再灌注损伤的影响

Effects of losartan on myocardial ischemia reperfusion injury in rats

目的:观察血管紧张肽II1型受体阻断剂 氯沙坦对大鼠缺血再灌注心肌的梗死面积、心肌结 构、肿瘤坏死因子α(TNF α)、白细胞介素6(IL 6) 的影响。方法:雄性Sprague Dawley(SD)大鼠42只 随机分为4组:对照组、缺血再灌注组、氯沙坦 5mg·kg-1组和氯沙坦10mg·kg-1组。除对照组 外,余3组建立心肌缺血再灌注模型,2个氯沙坦组 分别于缺血前15min静脉注射氯沙坦5,10mg· kg-1。计算心肌梗死范围,观察心肌细胞超微结构, 检测再灌注后血浆TNF α和IL 6的浓度。结果:与 缺血再灌注组相比,2氯沙坦组梗死面积减小(P< 0.01),心肌超微结构改善。缺血再灌注组TNF α 和IL 6的浓度均明显高于对照组(P<0.01);2个 氯沙坦组TNF α和IL 6的浓度均低于缺血再灌注 组(P<0.01),其中氯沙坦10mg·kg-1组较 5mg·kg-1组的浓度低(P<0.05,P<0.01)。结 论:氯沙坦具有抗大鼠心肌缺血再灌注损伤的作用, 高剂量氯沙坦的效果明显,其机制可能与从受体水 平阻断肾素 血管紧张肽系统,减少炎性因子TNF α和IL 6的产生有关。

AIM: To explore the effect of angiotensin II type 1 receptor antagonist losartan on the myocardial infarct size,the ultrastructure of myocardium,the production of tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) ,and to investigate the possible molecular protective mechanism of losartan on myocardial ischemia reperfusion(I/R) injury in rats. METHODS: Forty-two healthy male SD rats were divided into four groups:(1)Control group(n=6);(2)Ischemia reperfusion group(I/R group,n=12):the left coronary artery was occluded for 30 min to produce ischemia and then followed by 60 min reperfusion;(3)LOS 1 group(n=12):losartan (5 mg·kg -1,iv) was injected intravenously at 15 min before ischemia;(4)LOS 2 group(n=12):losartan (10 mg·kg -1,iv) was injected intravenously at 15 min before ischemia. At the end of reperfusion,the blood samples were collected and the plasma concentrations of TNF-α,IL-6 were measured with enzyme-linked immunosorbent assay(ELISA) system. The heart was harvested for determination of myocardial infarct size (by-TTC) and ultrastructure examination(through electron microscopy). RESULTS: The infarct size in groups LOS 1 and LOS 2 was significantly smaller than that in I/R group(P<0.01).Myocardial ultrastucture in groups LOS 1 and LOS 2 was well-preserved in comparing with that of I/R heart. After 60min reperfusion,the plasma concentrations of TNF-α and IL-6 were significently increased in comparing to that of I/R group(P <0.01). Losartan significantly decreased the serum levels of TNF-α and IL-6.The mean concentrations of these two cytokines in LOS 2 group were lower than those in LOS 1 group(P<0.05,P<0.01). CONCLUSION: Angiotensin II type I receptor antagonist losartan possesses cardioprotective effect on ischemia reperfusion myocardium in rats,the higher the dose of losartan the better the protective effect superion to the lower one.The mechanism may be involved in reducing the production of inflammatory cytokines(TNF-α,IL-6) during myocardial ischemia and reperfusion.