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OA
Mechanism of liquiritin in the improvement of ventricular remodeling after acute myocardial infarction via regulating the TXNIP/TRX signaling pathway
探究甘草苷(LQ)对改善急性心肌梗死(AMI)后心室重构(VR)的作用机制.分子对接预测甘草苷与硫氧还蛋白相互作用蛋白(TXNIP)的结合作用.冠状动脉左前降支结扎构建急性心肌梗死模型大鼠,造模 2周后,将造模成功的大鼠随机分为模型组、低剂量甘草苷组(20 mg/kg)和高剂量甘草苷组(40 mg/kg).甘草苷每天灌胃给药 1次,假手术组和模型组给予等体积的 0.5%羧甲基纤维素钠(CMC-Na)溶液,均连续干预 4周.超声心动图检测大鼠心脏功能,HE染色观察心脏病理变化,ELISA法检测大鼠血清肌酸激酶同工酶(CK-MB)活性,比色法检测大鼠血清丙二醛(MDA)、总超氧化物歧化酶(T-SOD)和过氧化氢酶(CAT)的活性.RT-qRCR法检测大鼠心肌组织中 TXNIP、硫氧还蛋白(TRX)、NOD样受体热蛋白结构域相关蛋白 3(NLRP3)的基因表达水平;Western blot法检测大鼠心肌组织中 TXNIP、TRX和 NLRP3蛋白表达水平.分子对接结果显示,甘草苷与 TXNIP靶点的结合较好.20、40 mg/kg甘草苷干预后,可明显升高射血分数(EF)和缩短分数(FS)水平(P<0.01),降低左心室收缩末期内径(LVIDs)、左心室舒张末期内径(LVIDd)、左心室收缩末期容积(LVESV)、左心室舒张末期容积(LVEDV)水平(P<0.01);心肌结构改善显著,细胞排列趋于规则,炎性细胞浸润和坏死面积缩小;显著降低了心肌酶 CK-MB水平(P<0.01);减少了血清中 MDA活性,提高了 CAT和 T-SOD活性(P<0.01).甘草苷有效抑制了AMI大鼠心肌组织中 TXNIP和 NLRP3的基因和蛋白的过度表达,同时促进了 TRX基因和蛋白表达(P<0.01).综上所述,甘草苷对TXNIP/TRX信号通路具有调控作用,抑制NLRP3炎症小体的激活,有效改善AMI后VR.
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.
邓义放;郭露琴;李自强;赵月月;袁瑛;王靓;周鹏
安徽中医药大学中西医结合学院,合肥 230012安徽中医药大学中西医结合学院,合肥 230012安徽中医药大学中西医结合学院,合肥 230012安徽中医药大学中西医结合学院,合肥 230012安徽中医药大学中西医结合学院,合肥 230012安徽中医药大学中西医结合学院,合肥 230012||中药复方安徽省重点实验室,合肥 230012安徽中医药大学中西医结合学院,合肥 230012||中药复方安徽省重点实验室,合肥 230012
医药卫生
甘草苷急性心肌梗死心室重构TXNIP/TRX信号通路NLRP3炎性小体
liquiritinacute myocardial infarctionventricular remodelingTXNIP/TRX signaling pathwayNLRP3 inflammasome
《中国药科大学学报》 2026 (3)
369-376,8
国家自然科学基金项目(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)and the Key Project Foundation of Natural Science Research in Universities of Anhui Province(2022AH050479)
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