乳酸和低剂量依达拉奉联合药物后适应减轻急性心肌梗死大鼠心肌再灌注损伤的研究

摘要

Objective The aim of this study was to test the hypothesis that pharmacological postconditioning with lactic acid and low dose of edaravone could mimic the upper trigger of mechanical postconditioning and attenuate myocardial reperfusion injury by ERK pathway. Methods 108 rats were randomly divided into 6 groups: sham, reperfusion/injury(R/I), postconditioning (Post), lactic acid (Lac), low dose of edaravone (Eda), and lactic acid+low dose of edaravone edaravone (Lac+Eda). After 10min of reperfusion, pH value of right atrial plasma was determined. Then the rats were sacrificed at different times, respectively, the content of myocardial MDA and SOD were measured (after 1 hour), the expression of phosphorylation of ERK1/2 (P-ERK) and cytochrome c (Cyt-c) in myocardial tissue were detected (after 6 hours), the content of myocardial enzyme in arterial blood were measured and myocardial apoptosis around infarction were detected (after 24 hours). Results Compared with Post group, pH of blood from right atrium in Lac and Lac+Eda group were similar (P>0.05);and the level of MDA and SOD in Eda and Lac+Eda group were also similar (P>0.05). The level of hemodynamic variables, serum marker of myocardium, apoptotic index, the expression of P-ERK and Cyt-c in Lac+Eda group were better than that of R/I group, and all similar with Post group(P>0.05). compared with R/I group, Lac and Eda group improved some indicators partially, but compared with Post group , still had obvious differences(P<0.05). Conclusions Pharmacological postconditioning with lactic acid and low dose of edaravone could mimic the upper trigger of mechanical postconditioning and attenuate myocardial reperfusion injury by ERK pathway.%目的：探讨乳酸和低剂量依达拉奉能否模拟机械后适应通过ERK途径减轻心肌细胞损伤。方法108只SD大鼠随机分为假手术、缺血再灌注（R/I）、后适应（Post，再灌注/缺血时间为20/20 s×4）、乳酸（Lac，微量注射器心肌注射乳酸）、低剂量依达拉奉（Eda，微量注射器心肌注射低剂量依达拉奉）和乳酸+依达拉奉组（Lac+Eda，微量注射器心肌注射乳酸和低剂量依达拉奉）6组。测定再灌注10 min后右心房血浆pH值，并在不同时间点处死大鼠，分别检测心肌组织MDA和SOD含量（1 h后），心肌组织中磷酸化ERK1/2（P- ERK）和胞质中细胞色素c（Cyt-c）的表达（6 h后），动脉血心肌酶含量和检测梗死周边心肌凋亡（24 h后）。结果与Post组相比，再灌注10 min后Lac+Eda组右心房血浆pH值相似（P＞0.05），再灌注1 h后Lac+Eda组MDA和SOD含量相似（P＞0.05）。Lac+Eda组较R/I组可显著改善血流动力学，减轻细胞凋亡和坏死，同时伴随P-ERK显著升高和Cyt-c表达显著减少（P＜0.05）；与Post组相比上述指标均无明显差异（P＞0.05）。Lac和Eda组在上述指标方面较R/I组部分改善，但与Post组相比仍有明显差异（P＜0.05）。结论局部注射乳酸和低剂量依达拉奉联合使用可较好模拟机械后适应，通过ERK途径减轻心肌细胞损伤。