中国病理生理杂志2026，Vol.42Issue(6)：1061-1070,10.DOI:10.3969/j.issn.1000-4718.2026.06.003
丹酚酸A经HSP70/HSP90α-PI3K/AKT信号轴减轻小鼠肝缺血再灌注损伤
Salvianolic acid A attenuates hepatic ischemia-reperfusion injury in mice via HSP70/HSP90α-PI3K/AKT signaling axis
摘要
Abstract
AIM:To investigate the potential targets and molecular mechanisms of salvianolic acid A(SaA)in alleviating hepatic ischemia-reperfusion injury(HIRI)in mice.METHODS:Differentially expressed genes(DEGs)associated with HIRI were identified using the GSE151648 dataset obtained from the Gene Expression Omnibus database.Network pharmacology analysis was conducted to predict potential targets of SaA,and molecular docking was performed to evaluate the binding affinity of SaA with heat shock protein 70(HSP70;encoded by HSPA1A)and HSP90α(encoded by HSP90AA1).A mouse model of HIRI was established,and the animals were randomly devided into five groups(n=5):sham group,model(HIRI)group,and low-,medium-and high-dose(5,10 and 20 mg/kg)SaA pretreatment groups.Se-rum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)levels were quantified.Histopathological changes in liver tissues were evaluated via HE staining.The expression levels of tumor necrosis factor-α(TNF-α),inter-leukin-1β(IL-1β)and IL-6 were assessed via ELISA and qRT-PCR.Protein expression levels of B-cell leukemia/lympho-ma-2(Bcl-2),Bcl-2-associated X protein(Bax),cleaved caspase-3,and key components of HSP70/HSP90α-phosphati-dylinositol 3-kinase(PI3K)/protein kinase B(PKB/AKT)signaling pathway were determined via Western blot analysis.RESULTS:A total of 21 HSP-related DEGs associated with HIRI were identified.Intersection analysis with the predicted targets of SaA revealed HSPA1A and HSP90AA1 as core targets.Molecular docking analysis demonstrated strong binding affinity between SaA and both proteins,with binding energies of-11.1 and-7.6 kcal/mol,respectively.In vivo experi-ments showed that medium-and high-dose SaA pretreatment significantly reduced serum ALT and AST levels,attenuated histopathological liver injury,and dose-dependently suppressed inflammatory cytokine release.These effects were associ-ated with the up-regulation of HSP70 and HSP90α,activation of PI3K/AKT signaling pathway,regulation of Bcl-2/Bax ra-tio,and inhibition of caspase-3 activation(P<0.05).CONCLUSION:Treatment with SaA dose-dependently mitigates HIRI in mice by concurrently targeting HSP70 and HSP90α,thereby activating PI3K/AKT signaling axis,suppressing in-flammatory responses,and attenuating hepatocyte apoptosis and necrosis.关键词
丹酚酸A/肝缺血再灌注损伤/热休克蛋白/PI3K/AKT信号通路Key words
salvianolic acid A/hepatic ischemia-reperfusion injury/heat shock proteins/PI3K/AKT signaling pathway分类
医药卫生引用本文复制引用
乔平平,阿力木·土拉宏,李乾龙,赵中荣,邵英梅..丹酚酸A经HSP70/HSP90α-PI3K/AKT信号轴减轻小鼠肝缺血再灌注损伤[J].中国病理生理杂志,2026,42(6):1061-1070,10.基金项目
国家自然科学基金资助项目(No.82360111) （No.82360111）
省部共建中亚高发病成因与防治国家重点实验室开放课题项目(No.SKL-HIDCA-2023-2) （No.SKL-HIDCA-2023-2）
第七师胡杨河市财政科技计划项目(No.2023A13) （No.2023A13）
