基于Nrf2/BNIP3通路探讨苓桂术甘汤改善心肌梗死诱导大鼠心力衰竭的作用及机制  

Effect of Linggui Zhugan Decoction on myocardial infarction induced heart failure in rats based on Nrf2/BNIP3 pathway and its mechanism

作　　者：王翔 莫佳佳 汤同娟 周鹏[4] 黄金玲[4] WANG Xiang;Mo Jia-jia;TANG Tong-juan;ZHOU Peng;HUANG Jin-ling(School of Nursing,Anhui University of Chinese Medicine,Hefei 230012,China;Hefei Institute of Pharmaceutical Industry Co.,Ltd,Hefei 230601,China;Anhui Province Engineering Technology Research Center of Pharmaceutical Re-innovation,Hefei 230601,China;College of Integrative Chinese and Western Medicine,Anhui University of Chinese Medicine,Hefei 230012,China)

机构地区：[1]安徽中医药大学护理学院,安徽合肥230012 [2]合肥医工医药股份有限公司,安徽合肥230601 [3]安徽省药物再创新工程技术研究中心,安徽合肥230601 [4]安徽中医药大学中西医结合学院,安徽合肥230012

出　　处：《中国药理学通报》2023年第12期2390-2397,共8页Chinese Pharmacological Bulletin

基　　金：国家自然基金面上项目(No 81973844);安徽省高校优秀人才支持项目(No gxyq2020020);安徽中医药大学青年科技英才培育项目(No 2021qnyc10);安徽中医药大学高层次人才支持计划项目(No 2022rcyb021)。

摘　　要：目的探讨苓桂术甘汤(Linggui Zhugan Decotion,LGZGD)抑制心室重构防治心梗后心衰的作用是否与调节Nrf2/BNIP3通路有关。方法冠脉结扎制备大鼠心梗后心衰模型,造模14 d后,随机分为模型组、苓桂术甘汤组、卡托普利组,另设假手术组,灌胃28 d,每天1次。超声心动图检测大鼠心功能;ELISA法检测血清BNP、NT-ProBNP含量;天狼星红染色观察大鼠心肌组织胶原纤维的变化;免疫荧光法检测大鼠心肌组织ROS的含量,微量法检测大鼠心肌组织SOD的含量,透射电镜观察线粒体超微结构,Western blot法检测CytC(线粒体、细胞质)、Nrf2(细胞质、细胞核)的表达,免疫荧光检测Nrf2、BNIP3蛋白的表达。结果苓桂术甘汤可以显著改善心梗后心衰大鼠的心功能,降低BNP、NT-ProBNP的含量,抑制心肌间质胶原的过度沉积,降低ROS,提高SOD的含量,改善线粒体结构损伤,并可上调Nrf2的表达及核移位,降低BNIP3的表达。结论苓桂术甘汤可有效抑制心梗后的心室重构阻抑心衰的发生发展,且其药效作用的发挥与调节Nrf2/BNIP3通路,减轻氧化应激损伤,保护线粒体,减少心肌细胞的凋亡有关。Aim To investigate whether Linggui Zhugan Decoction(LGZGD)can inhibit ventricular remodeling and prevent heart failure in rats after myocar-dial infarction by regulating Nrf2/BNIP3 pathway.Methods The model of heart failure after myocardial infarction was established by left coronary artery ligation in rats.Two weeks after modeling,all rats were randomly divided into model group,LGZGD group,and captopril group.Meanwhile sham operation group was set up.The rats were given continuous intragastric administration with drug or distilled water for 28 days,once a day.The behavioral signs of rats in each group were observed.The cardiac function of rats in each group was examined by echocardiography.Serum BNP and NT-ProBNP content were detected by enzyme-linked immunoassay;The changes of myocardial histopathological and collagen fibers in rats were detected using sirius staining.The contents of oxidative stress index including ROS,SOD in myocardial tissue of rats in each group were observed by DCFH-DA fluorescent probe and Enzyme-linked immunoassay.The ultrastructure of mitochondria was observed by transmission electron microscopy.Expressions of apoptotic proteins(mitochondrial CytC,cytoplasmic CytC)were detected by Western blot.Expression of proteins related to the Nrf2/BNIP3 pathway were examined by immunofluorescence and Western blot.Results LGZGD could significantly improve the cardiac function of rats,reduce the contents of BNP and NT-ProBNP,inhibit the excessive deposition of collagen in myocardial interstitium,reduce ROS,increase the content of SOD,improve mitochondrial structure damage,up-regulate the expression of Nrf2 and nuclear translocation,and reduce the expression of BNIP3.Conclusions LGZGD can inhibit the ventricular remodeling and prevent the occurrence of heart failure after myocardial infarction.Its pharmacological effects are mainly related to regulating the Nrf2/BNIP3 pathway,activating Nrf2,promoting its nuclear transfer,and further down-regulating BNIP3,protecting mitochondrial function,and reducing

关 键 词：苓桂术甘汤 心室重构 氧化应激 线粒体 凋亡 Nrf2/BNIP3通路 

分 类 号：R-332[医药卫生] R282.71R329.24R349.1R542.22R541.61