Urocortin-I通过激活Akt/GSK-3β改善I/R心肌单相动作电位及氧化炎症反应

Urocortin-I improves monophasic action potential and oxidative inflammation in I/R myocardium by activating Akt/GSK-3β pathway

目的研究Urocortin-I通过激活蛋白激酶B(Akt)/糖原合成酶激酶3β(GSK-3β)通路,对缺血再灌注(I/R)心肌单相动作电位及氧化炎症反应的作用。方法制备离体心肌Langendorff灌注模型,并分为对照组、I/R组、Urocortin-I组、Urocortin-I+LY组。对照组进行常规灌流;I/R组给予常规预处理、Urocortin-I组给予Urocortin-I预处理、Urocortin-I+LY组给予Urocortin-I+LY294002预处理后,均进行缺血再灌注处理。比较4组间心肌酶、心肌梗死面积、单相动作电位、炎症因子、氧化应激产物、Akt/GSK-3β通路分子的差异。结果与对照组比较,I/R组乳酸脱氢酶(LDH)、磷酸肌酸激酶同工酶(CK-MB)、肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、细胞间黏附分子1(ICAM-1)、活性氧簇(ROS)、丙二醛(MDA)的含量及心肌梗死面积明显增加,APA、APD50、APD90的水平及p-Akt、p-GSK-3β的含量明显减少(P<0.05)。与I/R组比较,Urocortin-I组LDH、CK-MB、TNF-α、IL-6、ICAM-1、ROS、MDA的含量及心肌梗死面积明显减少,APA、APD50、APD90的水平及p-Akt、p-GSK-3β的含量明显增加(P<0.05)。与Urocortin-I组比较,Urocortin-I+LY组LDH、CK-MB、TNF-α、IL-6、ICAM-1、ROS、MDA的含量及心肌梗死面积明显增加,APA、APD50、APD90的水平及p-Akt、p-GSK-3β的含量明显减少(P<0.05)。结论Urocortin-I通过激活Akt/GSK-3β通路改善I/R心肌的单相动作电位及氧化炎症反应。

Aim To explore the improvement effects of Urocortin-I on myocardial monophasic action potential and oxidative inflammatory response in ischemia-reperfusion(I/R)myocardium by activating Akt/GSK-3βpathway.Methods Langendorff perfusion model of isolated myocardium was prepared and then divided into control group,I/R group,Urocortin-I group and Urocortin-I+LY group.The control group was given routine perfusion,I/R group was given routine preconditioning,Urocortin-I group was given Urocortin-I preconditioning,Urocortin-I+LY group was given Urocortin-I and LY294002 preconditioning before ischemia-reperfusion.The differences of myocardial enzymes,infarct size,monophasic action potential,inflammatory factors,oxidative stress products and Akt/GSK-3βpathway molecules among the four groups were compared.Results Compared with the control group,the contents of LDH,CK-MB,TNF-α,IL-6,ICAM-1,ROS,MDA and the size of myocardial infarction significantly increased,while the levels of APA,APD50,APD90 and the expression of p-Akt,p-GSK-3βsignificantly decreased in the I/R group(P<0.05).Comparedwith the I/R group,the contents of LDH,CK-MB,TNF-α,IL-6,ICAM-1,ROS,MDA and the size of myocardial infarction significantly decreased,while the levels of APA,APD50,APD90 and the expressions of p-Akt,p-GSK-3βsignificantly increased in the Urocortin-I group(P<0.05).Compared with the Urocortin-I group,the contents of LDH,CK-MB,TNF-α,IL-6,ICAM-1,ROS,MDA and the size of myocardial infarction significantly increased,while the levels of APA,APD50,APD90 and the expressions of p-Akt,p-GSK-3βsignificantly decreased in the Urocortin-I+LYgroup(P<0.05).Conclusion Urocortin-I improves monophasic action potential and oxidative inflammation in I/R myocardium by activating Akt/GSK-3βpathway.