PPARγ激动剂吡格列酮对大鼠心肌缺血再灌注心肌细胞凋亡的影响

Effects of PPAR gamma agonist pioglitazone on myocardial apoptosis after myocardial ischemia reperfusion in rats

目的探讨过氧化物酶体增殖物激活受体γ(PPARγ)激动剂吡格列酮对大鼠心肌缺血再灌注(I/R)心肌细胞凋亡的影响及其作用机制。方法雄性6周龄Wistar大鼠48只被随机分为假手术组、模型组和干预组,每组16只。模型组和干预组建立I/R模型,干预组采用吡格列酮10 mg/(kg·d)进行预处理,连续1周;模型组和假手术组仅给予等量生理盐水。干预1周测定各组大鼠血清肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)、血浆肌钙蛋白I(c Tn I)、心肌匀浆液中丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、心肌细胞中钙含量、心肌细胞凋亡率、心肌细胞蛋白GRP78及caspase蛋白的表达情况。结果干预1周后,模型组和干预组大鼠的CK-MB、LDH、c Tn I、心肌匀浆液MDA、心肌细胞钙含量、心肌细胞凋亡率、心肌细胞蛋白GRP78及caspase蛋白水平均显著高于假手术组(P<0.05),模型组和干预组大鼠的心肌匀浆液SOD、GSH-Px显著低于假手术组(P<0.05),干预组的CK-MB、LDH、c Tn I、心肌匀浆液MDA、心肌细胞钙含量、心肌细胞凋亡率、心肌细胞蛋白GRP78及caspase蛋白水平显著低于模型组(P<0.05),干预组大鼠的心肌匀浆液SOD、GSH-Px显著高于模型组(P<0.05)。结论 PPARγ激动剂对I/R模型大鼠心肌具有一定的保护作用,其作用机制可能与降低细胞中钙含量、GRP78及caspase蛋白表达有关。

Objective To investigate the effect of PPARγagonist pioglitazone on myocardial cell apoptosis in rat ischemia-reperfusion(I/R)and its mechanism.Methods Totally 48 male Wistar rats aged 6 weeks were randomly divided into sham group,model group,and intervention group with 16 rats in each group.The rats in intervention group were pretreated with pioglitazone 10 mg/(kg·d)for 1 week,while the rats in model group and sham group were given only the same amount of normal saline.The I/R rat model was established in model group and intervention group.The serum levels of CK-MB,LDH,cTnI,MDA,SOD,GSH-Px,calcium content in cardiomyocytes,apoptosis rate of cardiomyocytes,expression of cardiomyocyte protein GRP78 and caspase protein were determined in each group.Results One week after intervention,CK-MB,LDH,cTnI,myocardial MDA content,myocardial calcium content,cardiomyocyte apoptosis rate,expression of cardiomyocyte protein GRP78 and caspase protein in model group and intervention group were significantly higher than those in sham group(P<0.05).SOD and GSH-Px in the myocardial homogenate in model group and intervention group were significantly lower than those in sham operation group(P<0.05).CK-MB,LDH,cTnI,myocardial MDA content,myocardial calcium content,cardiomyocyte apoptosis rate,cardiomyocyte protein GRP78 and caspase protein levels in intervention group were significantly lower than those in model group(P<0.05).The myocardial SOD and GSH-Px were significantly higher in intervention group than those in model group(P<0.05).Conclusion The protective effect of PPAR gamma agonist on the myocardium of I/R model rats may be related to the reduction of calcium content,the expression of GRP78 and caspase protein in the cells.