RESUMO
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.
RESUMO
Aim ToinvestigatewhethertheJAK2/STAT3 signaling pathway regulates prohibitin expres-sion to protect cardiomyocytes against hypoxia/reoxy-genation injury in hydrogen sulfide postconditioning. Methods Primaryculturedcardiomyocytesfromneo-natal rats were divided into 6 groups: control group ( Normal) , hypoxia/reoxygenation group ( H/R ) , hy-drogen sulfide postconditioning group ( NP) , hydrogen sulfide with AG490 group ( N + A ) , AG490 group ( AG) , DMSO group ( DMSO) . The survival percent-age of cardiomyocytes and the release of LDH were tested at pre-hypoxia and reoxygenation 2h. After reox-ygenation, cell apoptosis was detected by flow cytome-try. The expression of t-STAT3, p-SATAT3 and PHB were determined with Western blot analysis. Results No obvious changes were observed among the groups before hypoxia (P <0. 05). After reoxygenation 2h, compared with H/R group, NP group significantly im-proved the survival rate of cardiomyocytes ( P <0. 05 ) , inhibited the release of LDH and the myocardi-al apoptosis ( P <0. 05 ) , meanwhile up-regulated the p-STAT3 and PHB expression. However, AG490 abol-ished the cardioprotection offered by hydrogen sulfide postconditioning and the increase in p-STAT3 and PHB expression.Conclusion Hydrogensulfidepostcondi-tioning may protect cardiomyocytes against hypoxia/reoxygenation injury through the JAK2/STAT3 pathway upregulating the expression of prohibitin.