中国药科大学学报2026,Vol.57Issue(3):369-376,8.DOI:10.11665/j.issn.1000-5048.2025072505
甘草苷调控TXNIP/TRX信号通路改善大鼠急性心肌梗死后心室重构的机制研究
Mechanism of liquiritin in the improvement of ventricular remodeling after acute myocardial infarction via regulating the TXNIP/TRX signaling pathway
摘要
Abstract
This study aimed to investigate the mechanism of liquiritin(LQ)in the improvement of ventricular remodeling(VR)after acute myocardial infarction(AMI).Molecular docking was used to predict the binding affinity of liquiritin to thioredoxin-interacting protein(TXNIP).After 2 weeks of modeling,the rats were randomly divided into a model group,a low-dose liquiritin group(20 mg/kg LQ),and a high-dose liquiritin group(40 mg/kg LQ).Liquiritin was administered by gavage once a day,and the sham group and model group were g iven the same volume of 0.5%sodium carboxymethylcellulose(CMC-Na),with intervention of 4 consecutive weeks.Echocardiography was employed to detect the cardiac function,HE staining was used to observe cardiological changes,ELISA was used to detect the activity of serum creatine kinase-MB(CK-MB)activity,and the colorimetric method was adopted to detect serum malondialdehyde(MDA),total superoxide dismutase(T-SOD)and catalase(CAT)activities.RT-qPCR was used to detect the gene expressions of TXNIP,thioredoxin(TRX)and NACHT,LRR,and PYD domains-containing protein 3(NLRP3).Western blot was used to detect the protein expressions of TXNIP,TRX and NLRP3 in rat myocardial tissue.Molecular docking results showed that liquiritin had a good binding affinity to TNXIP target.After 20 and 40 mg/kg liquiritin intervention,the levels of ejection fraction(EF)and fractional shortening(FS)were significantly increased(P<0.01),and the levels of LVIDs,LVIDd,LVESV,and LVEDV were decreased(P<0.01).The myocardial structure was significantly improved,the cell arrangement tended to be regular,and the area of inflammatory cell infiltration and necrosis was reduced.Liquiritin significantly reduced the level of CK-MB(P<0.01),decreased the activity of MDA,and increased the activities of CAT and T-SOD(P<0.01).Liquiritin effectively inhibited the overexpression of TXNIP and NLRP3 genes and proteins,and enhanced the expression of TRX genes and proteins in the myocardial tissues of AMI rats.In conclusion,liquiritin has a regulatory effect on the TXNIP/TRX signaling pathway,inhibits the activation of the NLRP3 inflammasome,and thus improves ventricular remodeling after acute myocardial infarction.关键词
甘草苷/急性心肌梗死/心室重构/TXNIP/TRX信号通路/NLRP3炎性小体Key words
liquiritin/acute myocardial infarction/ventricular remodeling/TXNIP/TRX signaling pathway/NLRP3 inflammasome分类
医药卫生引用本文复制引用
邓义放,郭露琴,李自强,赵月月,袁瑛,王靓,周鹏..甘草苷调控TXNIP/TRX信号通路改善大鼠急性心肌梗死后心室重构的机制研究[J].中国药科大学学报,2026,57(3):369-376,8.基金项目
国家自然科学基金项目(No.82004180) (No.82004180)
安徽省高等学校科学研究项目(自然科学类)重点项目(2022AH050479) This study was supported by the National Natural Science Foundation of China(No.82004180) (自然科学类)
and the Key Project Foundation of Natural Science Research in Universities of Anhui Province(2022AH050479) (2022AH050479)