PI3 K/Akt/Sirt1 signaling pathway mediated hydrogen sulfide postconditioning-induced protection against I/R injury
10.3969/j.issn.1001-1978.2016.02.023
- VernacularTitle:PI3 K/Akt/Sirt1信号通路介导硫化氢后处理对大鼠缺血心肌的保护作用
- Author:
Mingzhu HU
;
Bo ZHOU
;
Qiong SHENG
;
Bin DU
;
Junliang CHEN
;
Qingfeng PANG
;
Yong JI
- Publication Type:Journal Article
- Keywords:
ischemia/reperfusion;
hydrogen sulfide;
postconditioning;
PI3 K/Akt;
Sirt1;
PGC-1α;
cardio-protection
- From:
Chinese Pharmacological Bulletin
2016;(2):268-273
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the role of PI3 K/Akt/Sirt1 pathway in cardioprotection of hydrogen sulfide ( H2 S ) postconditioning against ischemia/reperfusion ( I/R) injury. Methods Langendorff perfusion appa-ratus was used to build an isolated rat myocardial I/R model. Isolated rat hearts were subjected to 30 min global ischemia followed by 60 min reperfusion after 20 min of equilibrium. 60 male SD rats were randomly di-vided into 5 groups(n=12):control group(Control), ischemia/reperfusion group( I/R) , H2 S postcondition-ing group( H2 S) , inhibitor LY294002 group( LY) and H2 S with inhibitor group( H2 S+LY) . The left ventric-ular diastolic pressure ( LVEDP ) , the left ventricular developed pressure(LVDP), the maximum rate of in-crease or decrease of left ventricular pressure ( ± dp/dtmax ) were registered at the end of 20 min equilibri-um, 30 and 60 min of reperfusion separately. Triphe-nyl tetrazolium chloride( TTC) staining was used to de-termine the myocardial infarct size. The levels of Sirt1 and PGC-1 mRNA were tested using real-time PCR. The expressions of Sirt1 and PGC-1αwere detected with Western blot analysis. Immunohistochemical method was used to determine the location of Sirt1 . Results There were no differences in equilibrium hemodynamics observed between the experimental groups(P>0. 05). At the end of reperfusion, compared with I/R group, H2 S group had obviously ameliorated functional recov-ery and significantly decreased the myocardial infarct size(26. 9 ± 4. 9)% vs(48. 9 ± 5. 6)%(P <0. 05). Meanwhile, the expression of Sirt1 and PGC-1α in-creased significantly. However,LY294002 reversed the cardioprotective effects provided by hydrogen sulfide postconditioning and reduced the level of Sirt1 and PGC-1α, the percentage of Sirt1-positive nuclei. Con-clusion PI3 K/Akt/Sirt1 signaling pathway mediates the hydrogen sulfide postconditioning-induced protec-tion against I/R injury.
