中国病理生理杂志2025，Vol.41Issue(3)：463-471,9.DOI:10.3969/j.issn.1000-4718.2025.03.006
SIRT1通过Wnt/β-catenin通路抑制D-半乳糖诱导的心肌细胞衰老和凋亡
SIRT1 inhibits D-galactose-induced cardiomyocyte aging and apoptosis through Wnt/β-catenin pathway
摘要
Abstract
AIM:To investigate the effect of silent information regulator 1(SIRT1)on the degree of aging and apoptosis in a mouse cardiomyocyte aging model through the regulation of Wnt/β-catenin pathway.METHODS:An in vi-tro aging model was established by inducing HL-1 cells with 40 µmol/L D-galactose(D-Gal).The HL-1 cells were trans-fected with a lentivirus overexpressing SIRT1,and the transfection efficiency was verified by Western blot.Western blot was used to detect the protein expression levels of SIRT1,P53,P21,cleaved caspase-3,B-cell lymphoma-2(Bcl-2),Bcl-2-associated X protein(Bax),β-catenin,Wnt3a and c-Myc.Senescence-associated β-galactosidase(SA-β-Gal)staining was used to detect cellular senescence level.MTT colorimetric assay was used to detect the cell viability,and flow cytometry was used to detect the apoptosis.RESULTS:Treatment of HL-1 mouse cardiomyocytes with D-Gal led to in-creases in the expression levels of aging-related proteins P53 and P21,as well as an increase in SIRT1 protein level.Addi-tionally,the SA-β-Gal staining showed a significant increase in the positive area(P＜0.05).The expression levels of apop-tosis-related proteins cleaved caspase-3 and Bax were elevated,while the level of the anti-apoptotic protein Bcl-2 was re-duced(P＜0.05).There was a marked decrease in cell viability(P＜0.05),and flow cytometry analysis demonstrated a significant increase in cell apoptosis rate(P＜0.05),which was positively correlated with the duration of D-Gal treatment.Overexpression of SIRT1 notably reduced both aging and apoptosis levels after 48 h of D-Gal treatment(P＜0.05).After D-Gal treatment,the expression levels of β-catenin,c-Myc and Wnt3a proteins were up-regulated.However,these levels were reduced when SIRT1 was overexpressed.Moreover,the addition of LiCl,a Wnt/β-catenin pathway agonist,resulted in increased expression levels of β-catenin,c-Myc and Wnt3a proteins compared with the group with SIRT1 overexpres-sion and D-Gal treatment(P＜0.05).CONCLUSION:SIRT1 inhibits cardiomyocyte apoptosis and alleviates cardiomyo-cyte aging through the Wnt/β-catenin pathway.关键词
沉默信息调节蛋白1/心肌细胞/细胞凋亡/细胞衰老/Wnt/β-catenin信号通路Key words
silent information regulator 1/cardiomyocytes/apoptosis/cellular senescence/Wnt/β-catenin signaling pathway分类
临床医学引用本文复制引用
陈瑞雪,庞淑瑾,陈鑫,郭依宁,方红城,吕洪雪,王陵军..SIRT1通过Wnt/β-catenin通路抑制D-半乳糖诱导的心肌细胞衰老和凋亡[J].中国病理生理杂志,2025,41(3):463-471,9.基金项目
广东省自然科学基金资助项目(No.2023A1515010282) （No.2023A1515010282）
广东省基础与应用基础研究基金联合基金资助项目(No.2023A1515110747) （No.2023A1515110747）
东莞市社会发展科技项目高水平医院建设专项(No.20231800923372) （No.20231800923372）
东莞市社会发展科技项目(No.20211800904402) （No.20211800904402）
