Protective Effect of CTRP6 on Doxorubicin-induced Cardiomyocyte Injury
10.11969/j.issn.1673-548X.2024.06.006
- VernacularTitle:CTRP6对阿霉素诱导的心肌细胞损伤的保护作用
- Author:
Rong HUANG
1
;
Chunyan KONG
;
Zhuoyu SHEN
Author Information
1. 430060 武汉大学人民医院心内科、代谢与相关慢病湖北省重点实验室
- Keywords:
CTRP6;
Apoptosis;
Oxidative stress;
Doxorubicin
- From:
Journal of Medical Research
2024;53(6):23-28
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the impact of C1q/tumour necrosis factor-related protein 6(CTRP6)on doxorubicin(DOX)-induced apoptosis and oxidative stress injury of cardiomyocytes,along with its associated mechanism of action.Methods The H9C2 car-diomyocyte injury model was established by dividing the subjects into different groups.These groups included the control group(NS group),the DOX(1μmol/L)group,and the DOX(1μmol/L)group supplemented with CTRP6 at concentration gradients of 0.5 μg/ml,1μg/ml,3μg/ml,and 5μg/ml,respectively.After 24hours of culture,the survival rate of the cardiomyocytes was measured,the results showed that the highest increase in cardiomyocyte survival rate was observed at a CTRP6 concentration of 3 μg/ml,which was selected as the optimal concentration.Subsequently,the experimental groups of H9C2 cardiomyocytes consisted of the control group(NS group),the CTRP6 group,the DOX(1μmol/L)group,and the DOX(1μmol/L)group supplemented with CTRP6(3μg/ml)group.The impact of DOX stimulation on the transcriptional and translational levels of CTRP6 was assessed using fluorescence real-time quantitative polymer-ase chain reaction(RT-qPCR)and Western blot assay.Apoptosis levels were measured using Tunel assay,while enzyme-linked im-munosorbent assay(ELISA)kits were was used to detect the activity of cellular total glutathione peroxidase(GSH-Px)and superoxide dismutase(SOD),as well as the levels of malondialdehyde(MDA).Western blot assay was used to detect the any alterations in the lev-els of AdipoR1 protein and the protein expression of the protein kinase B/glycogen synthase kinase-3 β(Akt/GSK-3 β)signaling path-way.Results Compared with the control group(NS group),the expression levels of CTRP6 protein and mRNA were significantly de-creased in the DOX group(46.26％and 67.74％reduction,respectively,P＜0.05).In contrast,compared with DOX group,the DOX+CTRP6group showed a significant increase in CTRP6 protein expression levels(P＜0.05).Among the different concentrations of CTRP6 added to the DOX+CTRP6group,the survival rate of cardiomyocytes in DOX+3μg/ml CTRP6 treatment group was significantly increased by 26.48％(P＜0.05).Tunel staining revealed a decrease in apoptosis and an upregulation of Bcl-2 expression.In addi-tion,GSH-Px and SOD activities increased by 20.49％and 36.89％respectively,while MDA levels were significantly inhibited(de-creased by 47.09％,P＜0.05).The levels of AdipoR1 protein was significantly increased(P＜0.05).Furthermore,there was a signifi-cant elevation observed in the phosphorylation levels of the Akt/GSK-3β signaling pathway proteins.Conclusion CTRP6 ameliorates DOX-induced apoptosis and oxidative stress injury in cardiomyocytes,possibly through the protective effect of the Akt/GSK-3β signa-ling pathway.
