Dexmedetomidine mitigating hypoxia/reoxygenation injury in H9C2 cardiomyocytes via STAT3/FoxO3a signaling pathway
Objective To establish a hypoxia/reoxygenation(H/R)model using rat cardiomyocyte line H9C2 cells to thoroughly investigate the regulatory role of STAT3/FoxO3a signaling pathway in the protective effects of dexmedetomidine(Dex)against H/R injury in cardiomyocytes.Methods The study was conducted at Shenzhen Research Institute Laboratory,the University of Hong Kong from July to November 2023.Logarithmically growing H9C2 cardiomyocytes were used for the experiments,and they were divided into different groups:a control group(group C),a hypoxia/reoxygenation group(group H/R,with 6 hours of hypoxia followed by 12 hours of reoxygenation),a Dex pretreatment followed by H/R group(group D),and a STAT3 inhibitor Stattic plus Dex pretreatment followed by H/R group(group S).The cell viability was detected by the CCK8 kit,the degree of cell injury was detected by lactate dehydrogenase(LDH)kit,the oxidative stress level was detected by malondialdehyde(MDA)kit,and the related protein expressions were detected by Western blot.One-way analysis of variance was used.Results The cell viability,Bcl-2 and P62 protein levels of H9C2 cells in group H/R were lower than those in group C,and the protein levels of LDH,MDA,Bax,CC-3,LC3 and Beclin-1 were higher than those in group C(all P＜0.05).The cell viability,P-STAT3/STAT3 ratio and the protein levels of Bcl-2,P62 and FoxO3 a in group D were higher than those in group H/R,while the contents of LDH and MDA and the protein levels of Bax,CC-3,LC3 and Beclin-1 were lower than those in group H/R(all P＜0.05).STAT3 inhibitor can attenuate the protective effect of Dex on myocardial cell injury.Conclusion Dex preconditioning inhibited the apoptosis and autophagy of cardiomyocytes through STAT3/FoxO3a signal pathway,reduced the oxidative stress level,attenuated the H9C2 cell damage caused by H/R,and thus alleviated myocardial ischemia-reperfusion injury.
DexmedetomidineMyocardial ischemia-reperfusion injurySTAT3/FoxO3a signal pathwayHypoxia/reoxygenationApoptosis
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