摘要
目的:探讨苦参碱对AMP活化蛋白激酶(AMPK)/沉默信息调节因子2相关酶3(SIRT3)信号通路的调控作用,以及对高脂饮食诱导肥胖症大鼠心功能的保护作用。方法:选取SD大鼠若干,其中10只大鼠作为空白组,其余大鼠建立高脂饮食诱导肥胖症大鼠模型。造模结束后,将50只模型大鼠随机分为模型组,二甲双胍组(20 mg/kg),苦参碱低(7.5 mg/kg)、中(15 mg/kg)和高(30 mg/kg)剂量组,每组10只,连续给药6周。开始给药时与实验结束后各称取1次体重;实验结束后麻醉大鼠,检测心功能指标水平;取静脉血检测空腹血糖(FBG)和空腹胰岛素(FINS)水平;处死大鼠,分离左心室心肌组织进行麦胚凝集素染色,观察各组大鼠心肌细胞表面积;采用蛋白质印迹法检测心肌组织中p-AMPK、AMPK和SIRT3蛋白表达水平。结果:实验结束后,与空白组比较,模型组大鼠体重、心肌细胞表面积明显增加,左心室收缩末期内径(LVESD)、左心室舒张末期内径(LVEDD)、左心室舒张末期容积(LVEDV)和左心室收缩末期容积(LVESV)明显升高,FBG、FINS水平明显升高,左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)和心肌组织中p-AMPK/AMPK、SIRT3蛋白表达水平明显降低,差异均有统计学意义(P<0.05)。与模型组比较,二甲双胍组和苦参碱各剂量组大鼠的体重、心肌细胞表面积明显降低,LVESD、LVEDD、LVEDV和LVESV水平明显降低,FBG、FINS水平明显降低,LVEF、LVFS和心肌组织中p-AMPK/AMPK、SIRT3蛋白表达水平明显升高,差异均有统计学意义(P<0.05)。与二甲双胍组比较,苦参碱低、中剂量组大鼠的体重、心肌细胞表面积明显增加,LVESD、LVEDD、LVEDV和LVESV水平明显升高,FBG、FINS水平明显升高,LVEF、LVFS和心肌组织中p-AMPK/AMPK、SIRT3蛋白表达水平明显降低,差异均有统计学意义(P<0.05);苦参碱高剂量组与二甲双胍组大鼠上述指标水平比较,差异均无统计学意义(P>0.05)。结论:苦参碱可减�
OBJECTIVE:To probe into the regulatory effectw of matrine on the AMP-activated protein kinase(AMPK)/silence information regulatory 2-related enzyme 3(SIRT3)signaling pathways and its protective effect on heart function in obese rats induced by high-fat diet.METHODS:A number of SD rats were selected,of which 10 rats were used as the blank group and the remaining rats were used to establish high-fat diet-induced obese rat model.After modeling,50 model rats were randomly divided into the model group,metformin group(20 mg/kg)and low-dose(7.5 mg/kg),medium-dose(15 mg/kg)and high-dose(30 mg/kg)matrine group,with 10 rats in each group,and administered continuously for 6 weeks.The rats were weighed at the beginning and the end of experiment;the rats were anesthetized to detect cardiac function at the end of the experiment;venous blood was obtained to detect fasting blood glucose(FBG)and fasting insulin(FINS);myocardial tissues of the left ventricle were isolated for wheat germ agglutinin staining and the surface area of myocardial cells in each group was observed.Western blotting was adopted to detect the expression of p-AMPK.AMPK and SIRT3 protein.RESULTS:At the end of experiment,compared with the blank group,rats in the model group had significantly increased body weight and surface area of myocardial cells,significantly elevated left ventricular end-systolic dimension(LVESD),left ventricular end-diastolic dimension(LVEDD),left ventricular end-diastolic volume(LVEDV)and left ventricular end-systolic volume(LVESV),significantly elevated FBG and FINS contents,significantly lower left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS)and p-AMPK/AMPK and SIRT3 protein expression in myocardial tissue,with statistically significant differences(P<0.05).Compared with the model group,the rats in metformin group and different doses of matrine groups had significantly lower body weight and surface area of myocardial cells,significantly lower LVESD,LVEDD,LVEDV and LVESV,significantly lower FBG and FINS
作者
盛蓉辉
张松
王丽娟
SHENG Ronghui;ZHANG Song;WANG Lijuan(Dept.of Cardiology,Xi’an Children’s Hospital,Xi’an 710003,China;Dept.of Pharmacy,No.986 Hospital of Air Force,Xi’an 710032,China;Dept.of Infectious Disease,Xi’an Children’s Hospital,Xi’an 710003,China)
出处
《中国医院用药评价与分析》
2022年第7期830-834,共5页
Evaluation and Analysis of Drug-use in Hospitals of China
基金
陕西省中医药管理局科研项目(No.2019-zz-zy017)。
