Asp基因对急性心肌梗死小鼠心功能及Erk1/2表达的影响

Effect of Asp gene on cardiac function and Erk1/2 expression in mice with acute myocardial infarction

目的探讨促酰化蛋白(Asp)基因对急性心肌梗死(MI)模型小鼠心功能的影响。方法将C57BL/6野生型小鼠及Asp^(-/-)小鼠各10只分为C57、Asp^(-/-)、C57+MI和Asp^(-/-)+MI组。结扎冠状动脉前降支24 h后行心脏B超检测心脏功能,留取心脏标本前测量小鼠空腹血糖及体质量。伊文思蓝-TTC染色观察存活心肌、缺血心肌和心梗心肌的面积。ELISA法测定白介素8(IL-8)、内皮型一氧化氮合酶(eNOS)及血脂谱的表达。Western blot测定细胞外信号调节蛋白激酶1/2(Erk1/2)和磷酸化p-Erk1/2蛋白的表达。结果Asp^(-/-)及Asp^(-/-)+MI组的空腹血糖及体质量均分别高于野生型组(P<0.05)。MI后Asp^(-/-)组小鼠的射血分数(EF)及短轴缩短率(FS)较野生型MI组小鼠降低,左心室舒张末内径(LVEDd)及左心室收缩末内径(LVESd)增加(P<0.05)。Asp^(-/-)+MI组缺血区面积明显大于C57+MI组小鼠(P<0.05)。与C57+MI小鼠相比,Asp^(-/-)+MI组小鼠IL-8升高。C57及Asp^(-/-)+MI组小鼠eNOS较术前均降低。Asp^(-/-)+MI组小鼠Erk1/2及p-Erk1/2明显弱于C57+MI组。结论Asp可能通过MAPK-Erk信号通路改善小鼠心功能、抑制心肌细胞凋亡和减轻小鼠心肌受损。

Objective To investigate the effect of acylation-stimulating protein(Asp)gene on cardiac function in mice with acute myocardial infarction(MI).Methods C57BL/6 wild-type mice and Asp^(-/-)mice were divided into four groups(C57,Asp^(-/-),C57+MI and Asp^(-/-)+MI)respectively.Twenty-four hours after ligation of the anterior descending coronary artery,heart B-ultrasound was performed to detect the cardiac function,and the fasting blood glucose and body weight of the mice were measured before thoracotomy sampling.Evans blue-TTC staining was used to observe the area of viable myocardium,ischemic myocardium and myocardial infarction.The expression of interleukin-8(IL-8),endothelial nitric oxide synthase(eNOS)and blood lipid profile was determined by ELISA.The expression of extracellular signal-regulated protein kinase 1/2(Erk1/2)and phosphorylated p-Erk1/2 protein was determined by Western blot.Results The fasting blood glucose and body weight of Asp^(-/-)control group and Asp^(-/-)myocardial infarction group were higher than those of wild-type group(P<0.05).After myocardial infarction,the EF and FS of the mice in the Asp^(-/-)group were lower than those in the wild-type myocardial infarction group,and the LVEDd and LVESd were increased(P<0.05).The ischemic area of Asp^(-/-)myocardial infarction group was significantly larger than that of wild-type myocardial infarction group(P<0.05).Compared with C57+MI mice,IL-8 in Asp^(-/-)myocardial infarction mice was elevated.The eNOS of wild-type and Asp^(-/-)myocardial infarction mice were lower than those before operation.Erk1/2 and p-Erk1/2 in Asp^(-/-)myocardial infarction group were significantly weaker than those in wild-type myocardial infarction group.Conclusions Asp gene may improve mouse cardiac function,inhibit myocardial apoptosis,and reduce myocardial damage in mice.