Effects of astragaloside on doxorubicin-induced myocardial injury via modulating apoptosis and autophagy sig-naling pathways
TAN Yan-ling
CHEN Hui
WEN Zhen-zhen
XIE Zhi-hai
ZHOU Zhi-cong
FENG Huan-cun
Abstract：Objective To evaluate the cardioprotective effect and underlying mechanisms of Astragaloside(AS)against doxorubicin(DOX)-induced myocardial injury in rats,and to observe changes at tissue and molecular levels,providing a theoretical basis for its clinical application.Methods A rat model of DOX-induced cardiotoxicity was es-tablished using a cumulative dose of 15 mg/kg.Rats were treated with either low or high doses of AS.Serum B-type na-triuretic peptide(BNP)levels were measured using ELISA.Myocardial collagen deposition was assessed by Masson stai-ning.The expression of apoptosis-and autophagy-related proteins(Bax,Bcl-2,Beclin1,Lamp1)was detected via Western blot.The effect of AS(0-1 000 ng/mL)combined with DOX on tumor cell proliferation was evaluated using CCK-8 assays.Kaplan-Meier survival curves were plotted for each group.Results Following DOX treatment(15 mg/kg),the 28-day survival rate of model rats was 10/18.Median survival times were 100 days(control),28.5 days(DOX),38.5 days(DOX+low-dose AS),and 71 days(DOX+high-dose AS),respectively.By day 7 post-modeling,BNP levels began to rise;on day 11,BNP levels in the control,DOX,DOX+low-dose AS,and DOX+high-dose AS groups were(662.92±18.61)pg/mL,(1 270.05±241.16)pg/mL,(1 235.02±163.76)pg/mL,and(951.06±44.33)pg/mL(F=13.656,P=0.002),respectively.Masson staining revealed significant collagen ac-cumulation in the DOX group,which was mitigated in the high-dose AS group.DOX upregulated Bax and Beclin1 ex-pression without affecting Bcl-2,whereas AS intervention reduced Bax and Beclin1 levels and increased Bcl-2 expres-sion.Lamp1 expression increased in a dose-dependent manner with AS.In vitro,AS(0-1 000 ng/mL)did not com-promise the antiproliferative effect of DOX on tumor cells after 24-72 h of co-treatment(F=1.461,0.276,0.585,P=0.285,0.885,0.681).Conclusion A cumulative dose of 15 mg/kg DOX effectively induces myocardial injury in rats.Conventional concentrations of AS do not interfere with the anticancer activity of DOX in vitro.High-dose AS[90 mg/(kg·day)]significantly attenuates myocardial apoptosis,BNP elevation,and collagen deposition,thereby im-proving survival in DOX-treated rats.The mechanism may be related to modulation of apoptosis and autophagy pathways in cardiomyocytes.
Keywords：Astragalosideadriamycinproliferationtumor
Publication Date：2025-06-15
Online Publishing Date：2025-08-18(First online date of this platform, not the publication date of the document)
Pages：5( 826-830 )