Resistin Promotes Cardiomyocyte Hypertrophy In Cultured H9c2 Cells Via Regulating AMPK/FOXO3a Signaling Pathway And Autophagy

Objective:The thesis is to discuss the effects of resistin on H9c2 cardiomyocyte hypertrophy and its possible underlying molecular mechanisms,that is via regulating AMPK/FOXO3 a signaling pathway and autophagy.Methods:H9c2 cardiomyocytes in good condition were selected and then cultured in medium containing 0.1% fetal bovine serum for 24 h's starvation.According to the objective of this experiment,all the groups were divided into two parts.The first part was divided into the following groups.Con group: control group;Res group: Resistin 50 ng/mL group;(Res +Met)group: resistin 50 ng/m L plus Metformin 2 mmol/L group;Met group: Metformin 2mmol/L group.The second part also contained four groups.Con group: control group;Res group: resistin 50 ng/mL group;(Res + Rap)group: resistin 50 ng/mL plus Rapamycin 100nmol/L group;Rap group: Rapamycin 100 nmol/L group.After several hours incubation,the changes of these cells were observed.The surface area of these cells was analyzed by using Image J software;the single-cell protein content was measured by BCA method;the relative expression of BNF and ?-MHC was detected by way of real-time quantitative PCR(RT-qPCR);and by use of Western Blot,protein expression of p-FOXO3a?p-AMPK?p-mTOR?FOXO3a?AMPK?mTOR and the expression quantity of Beclin1?LC3 were also measured.Results:(1)Resistin could significantly increase the cell surface area of H9c2 cardiomyocytes(4147±141.7 vs 7554±265.2,P<0.0001),promote protein level(330.6±23.68 vs438.1±22.55,P<0.05),up-regulate the expression of embryonic genes BNF and ?-MHC(P < 0.01),and AMPK agonist Metformin could restrain the above phenomenon(P <0.05).(2)With the resistin taking effect,the p-AMPK expression quantity reduced significantly compared with the Con group(P < 0.01),and the expression quantity of signaling molecule pFOXO3a?p-mTOR went up greatly(P < 0.01).After the intervention of Metformin,resistin was added,and compared with the Res group,the p-AMPK expression quantity went up largely(P < 0.05),and the expression quantity of signaling molecule pFOXO3a?p-mTOR reduced significantly(P < 0.05).(3)Being dealt with the resistin and compared with the Con group,expression quantity of Beclin1?LC3 reduced greatly(P < 0.01).After the intervention of Rapamycin expression quantity of Beclin1?LC3 went up largely compared with the Res group(P <0.05).Conclusion:(1)Resistin can promote cardiomyocyte hypertrophy in cultured myocardial H9c2 cells;(2)AMPK/FOXO3 a signal pathway has effect on cardiomyocyte hypertrophy induced by resistin;(3)Autophagy has effect on cardiomyocyte hypertrophy induced by resistin;(4)mTOR bridged of AMPK/FOXO3 a signaling pathway and autophagy in cardiomyocyte hypertrophy.To sum up,the whole progress can be concluded as: Resistin?p-AMPK??p-FOXO3a?? p-m TOR??autophagy?? cardiomyocyte hypertrophy.