吡格列酮保护大鼠心肌缺血再灌注损伤机制的研究

目的探讨吡格列酮保护大鼠心肌缺血再灌注损伤的机制,观察细胞外信号调节激酶1/2(ERK1/2)、低氧诱导因子-1α(HIF-1α)表达的变化。方法将SD大鼠30只随机分为5组:假手术组,缺血再灌注组,吡格列酮5mg组,吡格列酮10mg组和吡格列酮20mg组,每组6只,利用体内结扎左前降支的方法建立缺血再灌注损伤模型,Western blot法检测心肌组织ERK1/2、磷酸化ERK1/2的变化,RT-PCR法检测HIF-1α mRNA的变化。结果缺血再灌注组心肌组织ERK1/2表达较假手术组无变化,吡格列酮各组对其表达无影响;缺血再灌注组磷酸化ERK1/2表达上调,吡格列酮各组表达进一步上调,与吡格列酮剂量相关;缺血再灌注组HIF-1α mRNA表达上调,吡格列酮各组促进其进一步上调,与剂量无关。结论心肌缺血再灌注损伤时,机体可调动内源性生存激酶表达上调,应对急性损伤,吡格列酮可进一步促进这些激酶上调,发挥抗心肌缺血再灌注损伤作用。

The study on mechanism of protecting the myocardium from ischemia-reperfusion injury by pioglitazone

Objective To investigate the mechanism of protecting the myocardium from ischemia-reperfusion injury by pioglitazone,and to observe the changes of expression of ERK1/2 and HIF-1α.Methods Thirty rats were randomly divided into five groups:sham operation group(n=6),ischemia-reperfusion group(n=6),pioglitazone 5 mg treated group(n=6),pioglitazone 10 mg treated group(n=6)and pioglitazone 20 mg treated group(n=6).Left anterior descending coronary artery was ligated for 30 min and reperfused for 30 min to establish the model of ischemia-reperfusion.Western blot was performed to detect the expression of ERK1/2 and pERK1/2.RT-PCR was performed to detect the expression of HIF-1α mRNA.Results The expression of ERK1/2 in ischemia-reperfusion group was not changed after ischemia-reperfusion compared with sham operation group and pioglitazone treatment had no effect on it.The expression of pERK1/2 in ischemia-reperfusion group was upregulated after ischemia-reperfusion.The expression of pERK1/2 in pioglitazone 5 mg,10 mg and 20 mg treated groups was further upregulated in dose-dependent manner.The mRNA level of HIF-1α was also upregulated after ischemia-reperfusion and pioglitazone treatment could further upregulate it,but it was not dose-dependent.Conclusion Organism can mobilize endogenous survival kinases when ischemia-reperfusion occurs.Pioglitazone can further upregulate these kinases to protect the myocardium from ischemia-reperfusion injury.