桂枝甘草汤干预心肌缺血再灌注损伤大鼠心律失常的作用机制  

Effects Mechanism of Guizhi Gancao Decoction on Arrhythmia in Rats with Myocardial Ischemia/Reperfusion Injury

作　　者：王艳 高原[2,3] 朱明军 唐进法[2,3] 李彬 王贺[2,3] 曹英杰 崔琳[2,3] 王小晓 沈思[2] WANG Yan;GAO Yuan;ZHU Mingjun;TANG Jinfa;LI Bin;WANG He;CAO Yingjie;CUI Lin;WANG Xiaoxiao;SHEN Si(Henan University of Chinese Medicine,Zhengzhou 450000,Henan,China)

机构地区：[1]河南中医药大学,郑州450000 [2]河南中医药大学第一附属医院,郑州450000 [3]河南省中药安全评价与风险防控工程研究中心,郑州450000

出　　处：《中西医结合心脑血管病杂志》2023年第21期3901-3907,共7页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金青年基金项目(No.81503435);河南省中医管理局国家中医临床研究基地科研专项(No.2018JDZX058);河南省中医药科学研究专项课题(No.2022ZY2009);河南省中医药科学研究专项课题(No.20-21ZY2097);河南省中医药科学研究专项课题(No.2022ZY1021)。

摘　　要：目的:探讨桂枝甘草汤(GGD)干预心肌缺血再灌注(I/R)损伤大鼠心律失常的作用机制。方法:建立心肌I/R损伤大鼠模型,随机分为对照组、I/R组、GGD低剂量组、GGD高剂量组、美托洛尔组。观察并记录心肌I/R心律失常发生率和持续时间,进行心律失常评分;采用酶联免疫吸附试验(ELISA)法检测血清肌酸激酶同工酶(CK-MB)和肌钙蛋白I(cTnI)水平,分光光度法测定Na^(+)-K^(+)-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶水平,苏木精-伊红(HE)染色法观察心肌组织的病理学改变,免疫组化法检测心肌缝隙连接蛋白43(Cx43)表达,蛋白免疫印迹法(Western Blot)检测磷酸化Cx43(p-Cx43)和Kir2.1蛋白表达。结果:与对照组比较,I/R组大鼠室性期前收缩(VPC)次数明显增多,室性心动过速(VT)及心室纤颤(VF)的持续时间明显延长,心律失常评分增加,CK-MB和cTnI明显增高,而Na^(+)-K^(+)-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶活性、p-Cx43和Kir2.1蛋白表达降低,差异均有统计学意义(P<0.01);与I/R组相比,GGD低剂量组、GGD高剂量组和美托洛尔组CK-MB和cTnI降低,Na^(+)-K^(+)-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶活性增高,差异均有统计学意义(P<0.05或P<0.01);与I/R组相比,GGD高剂量组和美托洛尔组VPC发生次数减少,VT及VF持续时间缩短,心律失常评分降低,p-Cx43和Kir2.1蛋白表达升高,差异均有统计学意义(P<0.05或P<0.01)。结论:GGD可能通过改善Cx43的表达、提高Na^(+)-K^(+)-ATP酶和Ca^(2+)-Mg^(2+)-ATP酶活性及上调Kir2.1蛋白表达,从而发挥改善心肌I/R损伤大鼠室性心律失常发生的作用。Objective:To explore the effects mechanism of Guizhi Gancao Decoction(GGD)on arrhythmia in rats with myocardial ischemia-reperfusion(I/R)injury.Methods:The myocardial I/R rat models were established and randomly divided into 4 groups:control group,I/R group,GGD low-dose group,GGD high-dose group,and Metoprolol(Met)group.The incidence and duration of myocardial I/R arrhythmia were observed and recorded,and arrhythmia score was performed.Enzyme-linked immunosorbent assay(ELISA)method was used to determine serum creatine kinase-MB(CK-MB)and cardiac troponin I(cTnI).Na^(+)-K^(+)-ATPase and Ca^(2+)-Mg^(2+)-ATPase levels were detected by spectrophotometry.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of myocardial tissue.The expression of myocardial connexin 43(Cx43)was detected by immunohistochemistry.Phosphorylated Cx43(p-Cx43)and Kir2.1 protein expression were detected by Western Blot.Results:Compared with control group,the number of ventricular premature contractions(VPC),the duration of ventricular tachycardia(VT)and ventricular fibrillation(VF),arrhythmia score,CK-MB and cTnI significantly increased,while Na^(+)-K^(+)-ATPase and Ca^(2+)-Mg^(2+)-ATPase activities,p-Cx43 and Kir2.1 protein expressions decreased in I/R group,the differences were statistically significant(P<0.01).Compared with I/R group,the CK-MB and cTnI reduced,and Na+-K+-ATPase and Ca^(2+)-Mg^(2+)-ATPase activities were increased in GGD low-dose group,GGD high-dose group,and Met group,the differences were statistically significant(P<0.05 or P<0.01).Compared with I/R group,the occurrence of VPC in GGD high-dose group and Met group was decreased,the duration of VT and VF was shortened,the arrhythmia score was decreased,and the protein expressions of p-CX43 and Kir2.1 were increased,the differences were statistically significant(P<0.05 or P<0.01).Conclusion:GGD may improve the development of myocardial ischemia-reperfusion ventricular arrhythmia in I/R rats by improving Cx43 expression,enhancing Na^(+)-K^(+)-ATPase and Ca

关 键 词：心肌缺血再灌注 心律失常 桂枝甘草汤 缝隙连接蛋白43 实验研究 

分 类 号：R285.5[医药卫生—中药学]