吡格列酮经Ras依赖性途径保护缺血再灌注心肌细胞的实验研究

The Experimental Study of Protective Effects of Pioglitazone on Cardiomyocytes of Ischemia Reperfusion via a Ras-dependent Pathway

目的观察吡格列酮对缺血再灌注损伤心肌细胞的保护作用,并探讨其与Ras信号转导通路的关系。方法体外培养乳鼠心肌细胞,分正常对照组(Co组)、缺血再灌注组(I/R组)、吡格列酮预处理组(Pi组)、Ras抑制剂Manumycin组(Ma组)。采用MTT分析法测定各组心肌细胞活性;测定各组MDA、SOD、LDH、ATP含量。比较组间差异。结果与Co组比较,I/R组心肌细胞活性、SOD、ATP含量降低,MDA、LDH含量增加,差异有统计学意义(P<0.01);与I/R组比较,Pi组心肌细胞活性、SOD、ATP含量增加,MDA、LDH含量降低,差异有统计学意义(P<0.01);与Pi组比较,Ma组心肌细胞活性、SOD、ATP含量降低,MDA、LDH含量增加,差异有统计学意义(P<0.01)。结论吡格列酮预处理可减轻缺血再灌注心肌细胞损伤,保护机制与Ras信号转导通路有关。

Objective To observe the protective effect of Pioglitazone on myocardial cell of ischemia reperfusion injury and investigate its relationship with Ras signaling pathway.Methods The cardiomyocytes of neonatal rats were cultivated in vitro and divided into 4 groups：the control group（group Co）,ischemia reperfusion injury group（group I/R）,Pioglitazone preconditioning group（group Pi）,Manumycin group（the inhibitor of Ras）（group Ma）.MTT method was used to measure the viability of myocardial cells in each group.The contents of MDA,SOD,LDH and ATP in each group were detected.The differences between each group were compared.Results Compared with group Co,the viability of myocardial cells,the contents of SOD and ATP in group I/R were decreased,and the contents of MDA and LDH were increased.These differences were statistically significancant（P〈0.01）;Compared with group I/R,the viability of myocardial cells,the contents of SOD and ATP in group Pi were increased,and the contents of MDA and LDH were decreased.These differences were statistically significancant（P〈0.01）;Compared with group Pi,the viability of myocardial cells,the contents of SOD and ATP in group Ma were decreased,and the contents of MDA and LDH were increased.These differences were statistically significancant（P〈0.01）.Conclusion The preconditioning on ischemia reperfusion cardiomyocytes with Pioglitazone could reduce its injury through Ras signaling pathway.