益母草碱对压力超负荷心肌肥厚大鼠的作用及机制研究  

Effect and mechanism of leonurine on pressure overload-induced cardiac hypertrophy in rats

作　　者：丁晓丽 袁青青 薛丁嘉 杨福明 朱依谆[3] 钱海兵 DING Xiao-li;YUAN Qing-qing;XUE Ding-jia;YANG Fu-ming;ZHU Yi-zhun;QIAN Hai-bing(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Research Center for Consistency in Property and Effectiveness of Traditional Chinese Medicine,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Fudan University,Shanghai 201203,China)

机构地区：[1]贵州中医药大学,贵州贵阳550025 [2]贵州中医药大学道地药材性效用一致性研究中心,贵州贵阳550025 [3]复旦大学,上海201203

出　　处：《中国中药杂志》2022年第2期461-468,共8页China Journal of Chinese Materia Medica

基　　金：贵州省国际科技合作计划项目(黔科合外G字[2010]7012号);贵州省普通高等学校特色重点实验室项目(黔教合KY[2017]006);贵州省中医药管理局中医药、民族医药科学技术研究项目(QZYY-2015-118);贵阳中医学院大学生创新创业训练计划项目(贵中医大创合字[2015]2号)。

摘　　要：探讨益母草碱(leonurine,Leo)对腹主动脉缩窄(abdominal aortic constriction,AAC)致大鼠压力负荷型心肌肥厚的作用及作用机制。AAC方法建立压力超负荷大鼠心肌肥大模型,经益母草碱高、低剂量组(30、15 mg·kg^(-1))及阳性对照药氯沙坦钾片组(losartan,5 mg·kg^(-1))干预27 d后,采用血流动力学方法评价心功能,并记录左室收缩压(left ventricular systolic pressure,LVSP)、左心室舒张末压(left ventricular end-diastolic pressure,LVEDP)、左心室内压最大上升和下降速率(maximum increase and decrease in left ventricular pressure,±dp/dt_(max));采用心脏质量指数(heart weight index,HWI)和左室质量指数(left ventricular mass index,LVWI)测定左心室肥大程度;苏木精-伊红(HE)染色检测心肌组织变化和心肌细胞直径(the size of myocardial cell diameter,MD);ELISA法检测心肌组织中血管紧张素Ⅱ(AngⅡ)、血管紧张素Ⅱ1型受体(AT1R)含量;比色法检测心肌组织中Ca^(2+)水平;Western blot法检测磷脂酶C(PLC)、肌醇三磷酸(IP3)、AngⅡ、AT1R蛋白的表达;实时荧光定量PCR(real-time quantitative PCR,qRT-PCR)法检测β-肌球蛋白重链(β-MHC)、心房利钠因子(ANF)、AngⅡ、AT1R蛋白的表达。与模型组比较,益母草碱组可降低模型组大鼠LVSP、LVEDP、HWI、LVWI、MD的值,升高左心室±dp/dt_(max);改善心肌组织病理形态,减少心肌细胞的肥大、水肿及炎症细胞的浸润;降低心肌组织AngⅡ、AT1R和Ca^(2+)含量,降低心肌组织中PLC、IP3、AngⅡ、AT1R蛋白水平以及β-MHC、ANF、AngⅡ、AT1R、c-fos、c-myc mRNA表达。益母草碱可抑制AAC诱导的心肌肥大,其作用可能与肾素-血管紧张素(RAS)系统有关。To investigate the effects of leonurine(Leo)on abdominal aortic constriction(AAC)-induced cardiac hypertrophy in rats and its mechanism.A rat model of pressure overload-induced cardiac hypertrophy was established by AAC method.After 27-d intervention with high-dose(30 mg·kg^(-1))and low-dose(15 mg·kg^(-1))Leo or positive control drug losartan(5 mg·kg^(-1)),the cardiac function was evaluated by hemodynamic method,followed by the recording of left ventricular systolic pressure(LVSP),left ventricular end-diastolic pressure(LVESP),as well as the maximum rate of increase and decrease in left ventricular pressure(±dp/dt_(max)).The degree of left ventricular hypertrophy was assessed based on heart weight index(HWI)and left ventricular mass index(LVWI).Myocardial tissue changes and the myocardial cell diameter(MD)were measured after hematoxylin-eosin(HE)staining.The contents of angiotensinⅡ(AngⅡ)and angiotensinⅡtype 1 receptor(AT1 R)in myocardial tissue were detected by ELISA.The level of Ca^(2+) in myocardial tissue was determined by colorimetry.The protein expression levels of phospholipase C(PLC),inositol triphosphate(IP3),AngⅡ,and AT1 R were assayed by Western blot.Real-time quantitative PCR(qRT-PCR)was employed to determine the mRNA expression levels ofβ-myosin heavy chain(β-MHC),atrial natriuretic factor(ANF),AngⅡ,and AT1 R.Compared with the model group,Leo decreased the LVSP,LVEDP,HWI,LVWI and MD values,but increased±dp/dt_(max) of the left ventricle.Meanwhile,it improved the pathological morphology of myocardial tissue,reduced cardiac hypertrophy,edema,and inflammatory cell infiltration,decreased the protein expression levels of PLC,IP3,AngⅡ,AT1 R,as well as the mRNA expression levels ofβ-MHC,ANF,AngⅡ,AT1 R,c-fos,and c-Myc in myocardial tissue.Leo inhibited AAC-induced cardiac hypertrophy possibly by influencing the RAS system.

关 键 词：益母草碱 心肌肥厚 RAS系统 AngⅡ AT1R 

分 类 号：R285.5[医药卫生—中药学]