葛瑞林对慢性心力衰竭大鼠心肌组织及血液中TRX和ASK1表达的影响

Effect of Ghrelin on expression of TRX and ASK1 in myocardium and blood of chronic heart failure rats

目的探讨葛瑞林(Ghrelin)对慢性心力衰竭(CHF)大鼠心肌组织及血液中硫氧还蛋(TRX)和凋亡信号调节激酶1(ASK1)表达的影响。方法选择SD雄性大鼠60只,采用结扎左冠状动脉前降支建立大鼠CHF模型,按随机数字表法分为对照组和观察组,各30只。观察组给予尾静脉注射Ghrelin,对照组给予尾静脉注射0.9%氯化钠溶液。在第2、20、45天时,光镜和电镜观察各组大鼠心肌组织形态学及心肌细胞超微结构情况。第45天时,多道生理仪检测左心室功能的变化情况;免疫组化法检测TRX及p ASK1表达水平;RT-PCR检测TRX及ASK1mRNA表达水平。结果 HE染色在第2、20、45天时,对照组心肌细胞损伤均比观察组明显。第45天时,对照组心肌细胞超微结构损伤比观察组更明显;观察组左心室射血分数(EF)和左心室短轴缩短率(FS)较对照组高(均P<0.05);观察组ASK1免疫组化面积比和ASK1 mRNA表达水平均低于对照组,TRX免疫组化面积比和TRXmRNA表达水平明显高于对照组(均P<0.01)。结论 Ghrelin可下调CHF心肌组织中ASK1的表达,上调TRX表达,从而改善CHF心脏生物学功能。

Objective To investigate the effect of Ghrelin on the expression of thioredoxin （TRX） and apoptotic signal kinase 1 （ASK1） in myocardium and blood of chronic heart failure （CHF） rats.Methods CHF was induced by ligating the left anterior descending coronary artery in 60 male SD rats,then the CHF rats were randomly divided into two groups with 30 animals in each.CHF rats in study group were treated with intravenous injection of Ghrelin;those in control group were treated with intravenous injection of normal saline.The myocardium morphology and ultrastructure were observed by light and electron microscopy on d2,d20 and d45 after CHF induced;left ventricular function was evaluated by polygraphy;expression of TRX and ASK1 proteins in myocardial tissue were detected by immunohistochemistry;the expression of TRX and ASK1 mRNA was detected by RT-PCR.Results The myocardial injury of rats on d2,d20 and d45 after modeling in control group was more severe than that in study group.Electron microscopy also showed that the myocardial damage on d45 in control group was more severe than that in study group.（P〈0.05）;the left ventricular ejection fraction （LVEF） and left ventricular fraction shortening （LVFS） in study group were higher than those in the control group （P〈0.05）.The immunohistochemical ASK1 positive area and the expression ASK1 mRNA in myocardia tissue on d45 in the study group were lower than those in the control group,wile the immunohistochemical TRX positve area and the expression of TRX mRNA in myocardial tissue were significantly higher than those in the control group （P〈0.05）.Conclusion Ghrelin can downregulate ASK1 expression and upregulate TRX expression in CHF myocardium,and decrease the content of ASK1 and increase the content of TRX in the blood,so as to improve the biological function of CHF.