Spermidine Mediates Autophagy Through miR-451 to Alleviate Adriamycin-induced Cardiomyocyte Senescence
Objective To study the regulatory effect of spermidine(SPD)on miR-451-5p and the effect of autophagy media-ted by miR-451-5p on proliferation and apoptosis of aging cardiomyocytes.Methods Doxorubicin was used to treat H9C2 cells in rat myocardium,and cardiac senescence cell model was constructed.The cells were divided into Control group,Model group,negative control(NC)+SPD group and miR-451-5p Inhibitor+SPD group.Cardiac senescent cell models were constructed with adriamycin in all groups except Control group.After modeling,cells of NC+SPD group and Inhibitor+SPD group were trans-fected with miR-NC and miR-451-5p inhibitor,respectively,and treated with 10 μmol/L SPD for 24 h.CCK-8 was used to detect cell proliferative activity;β-galactosidase staining was used to detect myocardial senescence;Western blot was used to detect the protein expression of P21,a marker of aging in heart tissue;and qRT-PCR was used to detect mRNA expression of miR-451-5p and autophagy markers(LC3Ⅱ and Beclin1).Results Compared with normal H9C2 cells,the expression of miR-451-5p was lower in cardiac senescent cell models(P＜0.05).Compared with Control group,cell proliferation activity in Model group was decreased(P＜0.05),SA-β-gal positive staining area increased,and P21 protein expression was up-regulated(P＜0.05).The miR-451-5p expression,mRNA expressions of LC3 11 and Beclin1 were down-regulated(P＜0.05).Compared with model group,cell proliferation activity in NC+SPD group was increased(P＜0.05),SA-β-gal positive staining area decreased,and P21 protein expression was down-regulated(P＜0.05).The miR-451-5p expression,mRNA expressions of LC3 Ⅱ and Beclin1 were up-regulated(P＜0.05).Compared with NC+SPD group,cell proliferation activity of Inhibitor+SPD group was decreased(P＜0.05).SA-β-gal positive staining area increased,and P21 protein expression was up-regulated(P＜0.05).The miR-451-5p ex-pression,mRNA expressions of LC3 Ⅱ and Beclin1 were down-regulated(P＜0.05).Conclusion Spermidine can promote the proliferation and autophagy of cardiac senescence model cells by up-regulating the expression of miR-451-5p,thus alleviating the senescence of cardiomyocytes.
万方数据
维普
