Role of PI3K/Akt signaling pathway in sufentanil postconditioning-induced reduction of myocardial ischemia-reperfusion injury in rats: the relationship with mitochondrial permeability transition pore
10.3760/cma.j.issn.0254-1416.2017.05.027
- VernacularTitle:PI3K/Akt信号通路在舒芬太尼后处理减轻大鼠心肌缺血再灌注损伤中的作用:与线粒体通透性转换孔的关系
- Author:
Shouyuan TIAN
;
Wenjie ZHANG
;
Lixia NIE
;
Jiangang WANG
;
Jian ZHU
;
Xin WANG
- Keywords:
1-phosphatidlylinositol 3-kinase;
Protein-serine-threonine kinase;
Sufentanil;
Ischemic postconditioning;
Myocardial reperfusion injury;
Mitochondrial permeability transition pore
- From:
Chinese Journal of Anesthesiology
2017;37(5):613-617
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the mechanism underlying sufentanil postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats through evaluating the relationship between phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/Akt) signaling pathway and mitochondrial permeability transition pore (mPTP).Methods Forty-eight pathogen-free healthy male SpragueDawley rats,aged 3 months,weighing 250-300 g,were divided into 4 groups (n=12 each) using a random number table:sham operation group (group S),group I/R,sufentanil postconditioning group (group SP) and snfentanil postconditioning plus PI3K inhibitor wortmannin group (group SP +W).The rats were anesthetized with 20％ urethane 5 ml/kg.Myocardial I/R was induced by ligation of the anterior descending branch of left coronary artery for 30 min,followed by 120 min reperfusion.Sufentanil 1.0 μg/kg was injected via the sublingual vein at 5 min before reperfusion in SP and SP+W groups.Wortmannin 15 pμg/kg was injected via the sublingual vein at 5 min before reperfusion,and then sufentanil 1.0 μg/kg was given in group SP+W.Blood samples were taken from the abdominal aorta at the end of reperfusion for detection of serum cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) concentrations.The rats were then sacrificed and hearts were removed for determination of cell apoptosis (by TUNEL),nicotinamide adenine dinueleotide (NAD+) content (by speetrophotometry),and expression of phosphorylated Akt (p-Akt) in myocardial tissues (by Western blot).Apoptosis index (AI) was calculated.The myocardial mitochondria and cytoplasm were isolated for detection of the expression of cytochrome c (Cyt c) and apoptosis-inducing factor (AIF) using Western blot.Results Compared with group S,the serum cTnI and CK-MB concentrations and AI were significantly increased,the content of NAD+ was decreased,the expression of p-Akt was up-regulated,the expression of Cyt e and AIF in mitochondria was down-regulated,and the expression of Cyt c and AIF in cytoplasm was up-regulated in I/R,SP and SP+W groups (P＜0.05).Compared with group I/R,the serum cTnI and CK-MB concentrations and AI were significantly decreased,the content of NAD+ was increased,the expression of p-Akt was up-regulated,the expression of Cyt c and AIF in mitochondria was up-regulated,and the expression of Cyt c and AIF in cytoplasm was down-regulated in group SP (P＜0.05).Compared with group SP,the serum cTnI and CK-MB concentrations and AI were significantly increased,the content of NAD+ was decreased,the expression of p-Akt was down-regulated,the expression of Cyt c and AIF in mitochondria was down-regulated,and the expression of Cyt c and AIF in cytoplasm was up-regulated in group SP+W (P＜0.05).Conclusion Sufentanil postconditioning can activate PI3K/Akt signaling pathway,inhibit mPTP opening,mitigate mitochondrial injury and inhibit apoptosis in cardiomyocytes,thus attenuating myocardial I/R injury in rats.
