The Mechanism of Astragaloside on Myocardium Injury in Rats of Hypoxic-induced Heart Failure Based on HIFs/RhoB/ROCK Pathway
ZHANG Jia
QIN Rui
LI Gang
Abstract：Objective:To observe the effect of astragaloside(AST)on hemodynamic parameters,troponin and apoptosis in hypoxia-induced heart failure rats,and to explore the effect of AST by regulating hypoxia inducible factor(HIFs)/RhoB protein(RhoB)/Rho-associated kinase(ROCK)signaling pathway.Methods:The rat model of heart failure was established by injecting adriamycin hydrochloride into the tail vein.After AST treatment,the rats were treated with HIF-1α-interfering adenovirus(HIF-1αsiRNA)and HIF-2α-interfering adenovirus(HIF-2αsiRNA).The rats were divided into Sham group,heart failure group(HF group),HF+AST group,HF+AST+negative control group(HF+AST+NC group),HF+AST+siRNA HIF-1α group(HF+AST+siRNA HIF-1α group),heart failure+AST+siRNA HIF-2α group(HF+AST+siRNA HIF-2α group).The changes of cardiac troponin I(cTnI),heart rate,systolic blood pressure,diastolic blood pressure,and mean blood pressure(MBP)were measured and reactive oxygen species were detected by flow cytometry.The mRNA expressions of HIF-1α and HIF-2α were detected by Real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).The expressions of HIF-1α,HIF-2α,RhoB,and ROCK were detected by Western Blot.The expression level of Caspase-3 was detected by enzyme-linked immunosorbent assay(ELISA).Results:Compared with HF group,the heart rate,diastolic blood pressure,and MBP in the HF+AST group increased,the levels of cTnI,ROS and Caspase-3 decreased,the mRNA and protein expressions of HIF-1α and HIF-2α increased,and the protein expressions of RhoB and ROCK increased(P＜0.05).Compared with HF+AST+NC group,the heart rate,systolic blood pressure and MBP of rats in the HF+AST+siRNA HIF-1α group and HF+AST+siRNA HIF-2α group increased,and the levels of cTnI,reactive oxygen species and Caspase-3 significantly increased,the expression of RhoB and ROCK protein in cardiomyocytes decreased(P＜0.05).Conclusion:AST could attenuate cardiomyocyte injury in rats of hypoxic-induced heart failure,and the mechanism might be related to HIFs/RhoB/ROCK pathway.
Keywords：heart failurehypoxia-induced cardiomyocyte injuryastragalosidehypoxia inducible factorRhoB proteinRho related kinaseratsexperimental study
Publication Date：2025-03-25
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 863-868 )