吡格列酮保护大鼠心肌缺血再灌注损伤机制的研究  

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

作　　者：王浩[1] 叶平[1] 李宗斌[1] 李泱[1] 曹泽玲[1] 王琳[1] 

机构地区：[1]解放军总医院南楼心血管二科,北京100853

出　　处：《中华老年心脑血管病杂志》2008年第7期537-540,共4页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

摘　　要：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。Objective To investigate the mechanism of protecting the myocardium from ischemiareperfusion 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 rag, 10 mg and 20 mg treated groups was further upregulated in dosedependent 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.

关 键 词：心肌缺血 心肌再灌注损伤 丝裂原活化蛋白激酶3 吡格列酮 

分 类 号：R541[医药卫生—心血管疾病]