Role of PI3K/Akt or JAK/STAT-3 signaling pathways in reduction of myocardial ischemia-reperfusion injury by combination of limb ischemic and morphine postconditioning in rats
10.3760/cma.j.issn.0254-1416.2017.03.027
- VernacularTitle:PI3K/Akt或JAK/STAT-3信号通路在肢体缺血联合吗啡后处理减轻大鼠心肌缺血再灌注损伤中的作用
- Author:
Shiyu WANG
;
Xinlong CUI
;
Fushan XUE
;
Heping LIU
;
Ruiping LI
;
Gaopu LIU
;
Guizhen YANG
;
Chao SUN
;
Xu LIAO
- Keywords:
1-Phosphatidylinositol 3-kinase;
Protein-tyrosine kinases;
Extremities;
Morphine;
Myocardial reperfusion injury;
Postconditioning
- From:
Chinese Journal of Anesthesiology
2017;37(3):361-365
- CountryChina
- Language:Chinese
-
Abstract:
Objective To evaluate the role of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)or Janus kinase(JAK)/signal transducer and activator of transcription 3(STAT-3)signaling pathways in reduction of myocardial ischemia-reperfusion(I/R)injury by combination of limb ischemic and morphine postconditioning in rats.Methods Eighty SPF healthy male Sprague-Dawley rats,aged 8 weeks,weighing 280-320 g,were used in the study.Myocardial I/R was induced by occlusion of the left anterior descending branch of the coronary artery for 30 min followed by 120 min reperfusion.The rats were divided into 8 groups(n=10 each)using a random number table:I/R group,limb ischemic postconditioning group(LIP group),morphine postconditioning group(group MP),combination of limb ischemic and morphine postconditioning group(LIP+MP group)and signaling pathway blocker groups(I/Rb group,LIPb group,MPb group,LIP+MPb group).In I/R,LIP,MP and LIP+MP groups,the animals were sacrificed at the end of reperfusion,and myocardial specimens in ischemic and non-ischemic regions were obtained for determination of phosphorylated STAT-3(p-STAT-3),STAT-3,phosphorylated Akt(p-Akt)and Akt expression(by Western blot)and STAT-3 and Akt mRNA expression(by polymerase chain reaction).In I/Rb,LIPb,MPb and LIP+MPb groups,PI3K/Akt signaling pathway blocker LY294002 0.3 mg/kg was intravenously injected in 5 rats of each group,and JAK/STAT-3 signaling pathway blocker AG490 5 mg/kg was intravenously injected in the other 5 rats of each group.The animals were sacrificed at the end of reperfusion,and myocardial specimens in the ischemic region were obtained for determination of myocardial infarct size.Results Compared with I/R group,the p-STAT-3/STAT-3 ratio in LIP,MP and LIP+MP groups and p-Akt/Akt ratio in LIP+MP group were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).Compared with LIP and MP groups,the p-STAT-3/STAT-3 and p-Akt/Akt ratios were significantly increased,and the expression of STAT-3 and Akt mRNA was up-regulated in LIP+MP group(P<0.05).There was no significant difference in myocardial infarct size between the four groups when PI3K inhibitor LY294002 was applied(P>0.05).When JAK2 inhibitor AG490 was applied,the myocardial infarct size was significantly smaller in LIP+MPb group than in I/Rb,LIPb and MPb groups(P<0.05),and there was no significant difference in myocardial infarct size between I/Rb,LIPb and MPb groups(P>0.05).Conclusion Combination of limb ischemic and morphine postconditioning can enhance the activation of PI3K/Akt or JAK/STAT-3 signaling pathways,and the cardioprotection is dependent on the integrity of the PI3K/Akt signaling pathway and partially dependent on the integrity of the JAK/STAT-3 signaling pathway when applied in combination in rats.
