中国药理学通报2013，Vol.29Issue(2)：248-253,6.DOI:10.3969/j.issn.1001-1978.2013.02.23
PI3K/Akt调节线粒体Cx43蛋白表达在H2S后处理离体大鼠心肌中的保护作用
Cardioprotective effect of connexin 43 expression regulated by PI3K/Akt on hydrogen sulfide postconditioning in isolated ischemic and reperfused rat hearts
摘要
Abstract
Aim To investigate whether the PBK/Akt signaling pathway regulates connexin 43 expression to protect isolated rat hearts against ischemia/reperfusion ( I/R ) injury in hydrogen sulfide postconditioning. Methods Hearts of 56 male SD rats were isolated and linked to the Langendorff apparatus. They were randomly divided into 4 groups( n = 14): ischemia reper-fusion group ( I/R ), PBK/Akt signaling pathway inhibitor LY294002 group ( LY ), hydrogen sulfide post-conditioning group ( NP ), and hydrogen sulfide with to all the nuclei counted was used as apoptotic index ( AI ). The expression of total Cx43 and phosphoryla-tion Cx43 in mitochondria were determined with Western blot analysis at the end of reperfusion. Results No differences in baseline hemodynamics were observed a-mong the experimental groups ( P > 0. 05 ). After reperfusion, compared with I/R group, NP group had better hemodynamics; the myocardial infarct size and cardiocyte apoptotic index were much lower ( P < 0. 05 ); the expression of tCx43 ( total connexin 43 , tCx43 ) and pCx43 ( phosphorylated connexin 43, pCx43 ) in mitochondria increased significantly. How- LY294002 group( N + L ). The heart rate ( HR ) , the left ventricular diastolic pressure ( LVEDP ), the left ventricular developed pressure ( LVDP ), the maximum rate of increase or decrease of left ventricular pressure ( ± dp/dtmax ) were recorded at 20 min of equilibrium at 30 min of reperfusion and at the end of reperfusion, respectively. Myocardial infarct size was measured by triphenyltet tetrazolium chloride ( TTC ) staining. Myocardial TUNEL staining was determined by in situ cell death detection kit. The ratio of TUNEL positive nuclei ever , LY294002 abolished the cardioprotection offered by hydrogen sulfide postconditioning and the increase in tCx43 and pCx43 expression in mitochondria. Conclusion The PI3K/Akt pathway upregulates connexin 43 expression to protect isolated rat hearts against is-chemia/reperfusion ( I/R ) injury in hydrogen sulfide postconditioning.关键词
硫化氢/后处理/缺血/再灌注损伤/心肌保护/PI3K/Akt/线粒体缝隙连接蛋白Cx43Key words
hydrogen sulfide/ pos condi ioning / myocardial ischemia reperfusion injury/ cardiopro ec ion/ PI3 k signaling pa hway/ mi ochondrial connexin 43分类
医药卫生引用本文复制引用
张可璇,毛洪雅,孟雪,惠夏,张邓新,季永..PI3K/Akt调节线粒体Cx43蛋白表达在H2S后处理离体大鼠心肌中的保护作用[J].中国药理学通报,2013,29(2):248-253,6.基金项目
江苏省教育厅资助项目(N06KJD320186) （N06KJD320186）
徐州医学院院长基金资助项目(No N09K J Z02) （No N09K J Z02）
