芎归汤通过抑制氧化应激诱导的心肌凋亡减轻小鼠心梗后心衰引起的心肌损伤OA北大核心CSTPCDMEDLINE
Xionggui Decoction alleviates heart failure in mice with myocardial infarction by inhibiting oxidative stress-induced cardiomyocyte apoptosis
目的 基于网络药理学结合实验验证探索芎归汤对心梗后心衰小鼠心脏功能、心脏病理的改善及作用机制.方法 通过TCMSP、GeneCards、CTD等数据库搜索药物活性成分作用靶点与疾病相关靶点,并将二者取交集.采用DAVID数据库对交集靶点进行GO、KEGG通路富集分析.体内实验采用冠脉结扎构建心梗后心衰小鼠模型,分为假手术组(Sham,n=8)、模型组(Model,n=8)和芎归汤治疗组(XGT,3 g/kg,n=8).体外实验采用叔丁基过氧化氢诱导H9C2细胞凋亡,分为常规培养的对照组(Control)、叔丁基过氧化氢组(TBHP)、芎归汤低剂量组(XGT,50 μg/mL)和芎归汤高剂量组(XGT,100 μg/mL).通过HE、Masson、qPCR、免疫组化、CCK8、ROS、MDA、SOD、Hoechst 33342/PI和JC-1检测,探索芎归汤抗心衰的作用机制.结果 网络药理学分析结果显示,芎归汤治疗心衰的潜在作用靶点共 62个,其核心靶点包括PTGS2、ESR1、Caspase3、PPARG、HSP90AA1、BCL2、JUN、GSK3B等,富集分析显示这些靶点可能涉及细胞凋亡、AGE-RAGE信号通路、P53信号通路、PI3K-Akt信号通路、VEGF信号通路等.体内结果显示,芎归汤能够减少心衰小鼠心肌细胞损伤、减轻心室重构,从而改善心衰小鼠心功能(P<0.05).芎归汤能够抑制心肌凋亡相关蛋白Caspase3和BAX的表达,促进BCL2的表达(P<0.05).体外实验表明,芎归汤通过抑制氧化应激,从而减轻叔丁基过氧化氢诱导的心肌细胞凋亡(P<0.05).结论 芎归汤能减轻心梗后心衰引起的心肌损伤,改善心衰小鼠心功能,芎归汤可能通过抑制氧化应激诱导的心肌凋亡发挥抗心衰的作用.
Objective To explore the protective effect of Xionggui Decoction against cardiac myopathy in a mouse model of heart failure following myocardial infarction(MI)and explore the underlying mechanism.Methods We searched TCMSP,GeneCards,and CTD databases for the targets of active ingredients Xionggui Decoction and heart failure,and the intersecting targets were analyzed with GO and KEGG pathway enrichment analysis using DAVID database.In a mouse model of heart failure following acute MI induced by coronary artery ligation,the cardiac protective effects of 3 g/kg Xionggui Decoction were evaluated by assessing cardiac function,cardiac myopathy and ventricular remodeling of the mice using HE staining,Masson staining,RT-qPCR,and immunohistochemistry.We also tested the effect of Xionggui Decoction at 50 and 100 μg/mL on tert-butylhydrogen peroxide(TBHP)-induced apoptosis of H9C2 cells using CCK8 assay,detection kits for ROS,MDA,SOD,JC-1 and Hoechst 33342/PI staining.Results Network pharmacological analysis identified 62 potential targets of Xionggui Decoction for treatment of heart failure,and the core targets included PTGS2,ESR1,caspase-3,PPARG,HSP90AA1,BCL2,JUN,and GSK3B,which were involved in cell apoptosis and the AGE-RAGE,P53,PI3K-Akt,and VEGF signaling pathways.In the mouse models of heart failure,treatment with Xionggui Decoction significantly alleviated cardiac myopathy and ventricular remodeling,obviously improved heart function of the mice,lowered myocardial expressions of caspase-3 and BAX,and enhanced the expression of BCL2.In H9C2 cells,Xionggui Decoction significantly alleviated TBHP-induced cell apoptosis by inhibiting oxidative stress in the cells.Conclusion Xionggui Decoction can alleviate myocardial injury and improve cardiac function in mice with heart failure following acute MI possibly by inhibiting cardiomyocyte apoptosis induced by oxidative stress.
任志军;刁建新;王奕婷
东莞康华医院老年医学科,广东 东莞 523080南方医科大学中医药学院,广东 广州 510515
芎归汤心力衰竭网络药理学细胞凋亡氧化应激
Xionggui Decoctionheart failurenetwork pharmacologyapoptosisoxidative stress
《南方医科大学学报》 2024 (007)
1416-1424 / 9
广东省自然科学基金(2023A1515011200)
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