真武汤对慢性心力衰竭大鼠PINK1/parkin介导线粒体自噬的作用研究  

Study on the Effect of Zhenwu Tang on PINK1/Parkin Mediated Mitochondrial Autophagy in Rats with Chronic Heart Failure

作　　者：廖金花 王兴 王晓琳 陈智勇 车驰 单浩洪 李林[3,4] LIAO Jinhua;WANG Xing;WANG Xiaoling;CHEN Zhiyong;CHE Chi;SHAN Haohong;LI Lin(Guangzhou Zengcheng District Hospital of Traditional Chinese Medicine,Guangzhou 510000,China;Hunan Provincial Direct Affiliated TCM Hospital,Zhuzhou 412000,China;Jiangxi University of Chinese Medicine,Nanchang 330006,China;The Affiliated Hospital of Jiangxi University of TCM,Nanchang 330006,China)

机构地区：[1]广州市增城区中医医院,广州510000 [2]湖南省直中医医院,湖南株洲412000 [3]江西中医药大学,南昌330006 [4]江西中医药大学附属医院,南昌330006

出　　处：《中国中医基础医学杂志》2025年第1期43-48,共6页JOURNAL OF BASIC CHINESE MEDICINE

基　　金：国家自然科学基金项目(81960820);江西省自然科学基金项目(911198538072)。

摘　　要：目的从线粒体自噬探讨真武汤治疗慢性心力衰竭(chronic heart failure,CHF)大鼠的作用与机制。方法60只SD雄性大鼠随机分为6组:假手术组、模型组、氯沙坦组、真武汤6 g/kg组、真武汤12 g/kg组、真武汤18 g/kg组;采用左冠状动脉前降支(LAD)结扎法建立CHF大鼠模型。造模56 d后及灌胃28 d后分别行M型超声心动图(ME)检测大鼠心功能,ELISA检测血清B型钠尿肽(BNP)水平,HE染色法观察心脏组织改变,透射电镜观察心肌结构及线粒体超微结构改变,Western blot检测心脏组织中PTEN诱导假定激酶1(PINK1)、E3泛素连接酶(parkin)、磷酸化PINK1(p-PINK1)、磷酸化parkin(p-parkin)、微管相关蛋白1轻链3(LC3)、SQSTM1蛋白(p62)、苄氯素1(Beclin1)的蛋白表达水平及LC3Ⅱ/Ⅰ。结果与假手术组比较,模型组大鼠心脏收缩、舒张功能明显减弱(P<0.05),p-PINK1、p-parkin、Beclin1表达及LC3Ⅱ/Ⅰ明显下降(P<0.05),p62表达明显上升(P<0.05),心肌呈现小片状纤维化,心肌收缩带排列紊乱、线粒体基质变浅变少、线粒体出现空泡化改变;与模型组比较,真武汤6 g/kg组、真武汤12 g/kg组、真武汤18 g/kg组BNP水平及p62表达明显下降(P<0.05),p-parkin、p-PINK1、Beclin1表达及LC3Ⅱ/Ⅰ明显上升(P<0.05),心脏收缩、舒张功能明显改善(P<0.05),心肌纤维化程度下降,心肌排列较规则,线粒体基质饱满、线粒体嵴完整。结论真武汤能激活PINK1/parkin介导的线粒体自噬,提高受损线粒体内的物质利用,改善心肌的能量供应,改善CHF大鼠的心功能及心肌结构,抑制CHF的进程。Objective To explore the effects and mechanisms of Zhenwu Tang in treating chronic heart failure(CHF)rats from mitochondrial autophagy.Methods 60 SD male rats were randomly divided into 6 groups:sham-operated group,model group,Losartan group,Zhenwu Tang 6 g/kg group,Zhenwu Tang 12 g/kg group,Zhenwu Tang 18 g/kg group;and the rat model of CHF was established by using the ligation method of the anterior descending branch of the left coronary artery(left Anterior descending artery,LAD).After 56 days of model induction and 28 days of gavage,various tests were conducted to evaluate different aspects of cardiac function.M-mode echocardiography(ME)was used to assess cardiac function,ELISA was performed to measure serum B-type natriuretic peptide(BNP)levels,HE staining and transmission electron microscopy were employed to observe myocardial structure and mitochondrial ultrastructural changes.Additionally,Western blot analysis was conducted to detect the expression levels of PTEN-induced putative kinase 1(PINK1),E3 ubiquitin protein ligase(parkin),phosphorylated PINK1(p-PINK1),phosphorylated parkin(p-parkin),microtubule-associated protein 1 light chain(LC3),SQSTM1 protein(p62),and Beclin1 protein.Results Compared with the sham-operated group,the systolic and diastolic functions of the rat hearts in the model group were significantly attenuated(P<0.05).The expressions of p-PINK1,p-parkin and Beclin1 and LC3Ⅱ/Ⅰwere significantly decreased(P<0.05).While the expression of p62 was significantly increased(P<0.05),and the myocardium showed small-patch fibrosis,disorganised arrangement of myocardial contractile bands,and shallower and fewer mitochondrial matrix,Compared with the model group,BNP level and p62 expression were significantly decreased in Zhenwu Tang 6 g/kg group,Zhenwu Tang 12 g/kg group and Zhenwu Tang 18 g/kg group(P<0.05)The expression of p-parkin,p-PINK1 and Beclin1 as well as LC3Ⅱ/Ⅰincreased significantly(P<0.05),and the systolic and diastolic functions of the heart improved significantly(P<0.05).The sys

关 键 词：真武汤 心力衰竭 线粒体自噬 PINK1/parkin通路 

分 类 号：R285[医药卫生—中药学]