Role of AMPK/PGC-1αpathway in cardioprotection of hydrogen sulfide against ischemia/reperfusion injury
10.3969/j.issn.1001-1978.2015.07.013
- VernacularTitle:AMPK/PGC-1α信号通路在硫化氢抗心肌缺血/再灌注损伤中的作用
- Author:
Jieqiong YANG
;
Mingzhu HU
;
Bin DU
;
Junliang CHEN
;
Qingfeng PANG
;
Yong JI
- Publication Type:Journal Article
- Keywords:
ischemia/reperfusion;
hydrogen sulfide;
postconditioning;
cardioprotection;
AMP-activated pro-tein kinase;
peroxisome proliferator activated receptor gamma co-activator;
mitochondrial protection
- From:
Chinese Pharmacological Bulletin
2015;(7):951-956
- CountryChina
- Language:Chinese
-
Abstract:
Aim To explore the role of AMPK/ PGC-1α pathway in cardioprotection of hydrogen sulfide ( H2 S ) against ischemia/reperfusion ( I/R ) injury. Methods Langendorff perfusion apparatus was used to build an isolated rat myocardial I/R model. Seventy-two male SD rats were randomly divided into 6 groups (n=12):control group (Control), ischemia/reperfu-sion group ( I/R ) , DMSO group ( DMSO ) , inhibitor Compound C group ( CC) , H2 S postconditioning group ( NP) , and H2 S with Compound C group ( N +C ) . The heart rate ( HR ) , the left ventricular developed pressure ( LVDP ) , the maximum rate of increase or decrease of left ventricular pressure ( ± dp/dtmax ) and the left ventricular diastolic pressure ( LVEDP ) were registered at 20 min of baseline and 60 min of reperfu-sion separately. Triphenyl tetrazolium chloride ( TTC) staining and HE staining were used to determine the myocardial infarct size and the myocardial tissue mor-phological change of each group was observed respec-tively. Immunohistochemistry was used to determine the expression of PGC-1α. The expressions of total AMPK ( tAMPKα ) , phosphorylated AMPK ( pAMPKα) and PGC-1α were detected with Western blot anaylsis. Results There were no differences in e-quilibrium hemodyamics observed between the experi-mental groups(P>0. 05). At the end of reperfusion, compared with I/R group, NP group had obviously a-meliorated functional recovery and significantly de-creased myocardial infarct size [ ( 23. 9 ± 3. 4 )% vs (60. 9 ± 3. 8 )%, ( P <0. 05 ) ] . HE staining showed that in NP group, the myocardial injury was reduced. Meanwhile, the expression of pAMPKα and PGC-1αincreased significantly. However, Compound C re-versed the cardioprotection effects provided by hydro-gen sulfide postconditioning and reduced the expression of pAMPKαand PGC-1α. Conclusion AMPK/ PGC-1α pathway is involved in the role of hydrogen sulfide against ischemia/reperfusion injury.
