摘要
目的:研究芪苈参萸益心方对大鼠充血性心力衰竭(Congestive heart failure, CHF)的保护作用及可能的作用机制。方法:实验大鼠在成功进行冠脉结扎手术后,随机分为假手术组、模型组、芪苈参萸益心方28.8g/kg、57.6g/kg组、地高辛0.09mg/kg组;给药10周后,进行血流动力学测定,取血进行ROS、T-AOC、SOD、GSH-Px、CAT和MDA含量分析;心脏经TTC染色、HE和Masson染色,计算心肌梗死面积、心室扩张程度和心肌组织形态学观察,实时定量PCR和Western blot检测Sirt1/FoxO1/Pgc-1α和Nrf2/抗氧化通路相关基因表达。结果:芪苈参萸益心方28.8g/kg和57.6g/kg可显著改善CHF大鼠心功能,降低血液中ROS含量和MDA水平,增加T-AOC、SOD、GSH-Px、CAT酶的活性;减轻ROS所致心肌氧化应激损伤,降低心肌梗死面积、心室扩张程度和改善心脏组织形态学;上调心肌组织中Sirt1、胞核中Nrf2、Bcl-2蛋白表达和MnSOD、HO-1、NQO1、GCLC mRNA表达,下调Ac-FoxO1、Ac-Pgc-1α、Bax、cleaved-caspase-9、cleaved-caspas-3蛋白表达,升高Bcl-2/Bax比率。结论:芪苈参萸益心方对CHF具有较好的保护作用,激活Sirt1/FoxO1/Pgc-1α和Nrf2/抗氧化通路可能是其作用机制之一。
Objective:To study the protective effect and possible mechanism of Qilishenyuyixinfang on congestive heart failure(CHF)in rats.Methods:Coronary ligation surgery was used to establish the rat model,then all rats were randomly divided into the sham operation group,the model group,Qilishenyuyixinfang groups(28.8 g/kg and 57.6 g/kg)and 0.09 mg/kg digoxin group.After 10 weeks of administration,the hemodynamics was used to determine ROS,T-AOC,SOD,GSH-Px,CAT and MDA in serum.The myocardial infarction area,ventricular dilatation and myocardial histomorphology were calculated by TTC,HE and Mason staining in heart tissues.Real-time quantitative PCR and western blot were used to analyze the antioxidant pathway related factors Sirt 1/FoxO1/Pgc-1αand Nrf2.Results:Qilishenyuyixinfang(28.8 g/kg and 57.6 g/kg)significantly improved the cardiac function,reduced ROS content and MDA level in blood,increased the activity levels of T-AOC,SOD,GSH-Px and CAT,alleviated the oxidative stress injury induced by ROS,reduced the myocardial infarction area and ventricular dilatation and improved the cardiac tissue morphology in CHF rats.It also up-regulated Sirt1,nucleus Nrf2,Bcl-2 protein expressions in myocardial tissues and MnSOD,HO-1,NQO1,GCLC mRNA expressions,down regulated the expressions of Ac-FoxO1 and Ac-Pgc-1αprotein,increased Bcl-2/Bax ratioConclusion:Qilishenyuyixinfang has the good protective effect on CHF,its mechanism may be related to activating the Sirt1/FoxO1/Pgc-1 a and Nrf2/antioxidant pathways.
作者
张继红
卢超
石孟琼
向长青
陈腊年
任俊红
冯旻璐
许海燕
张媛媛
江伟杰
Zhang Jihong;Lu Chao;Shi Mengqiong;Xiang Changqing;Chen lanian;Ren Junhong;Feng Minlu;Xu Haiyan;Zhang Yuanyuan;Jiang Weijie(The Second people's Hospital,China Three Gorges University&The Second people's Hospital of Yichang;Medical Science College,China Three Gorges University,3 College of Biological and Pharmaceutical Sciences,China Three Gorges University,Yichang 443002)
出处
《中药药理与临床》
CAS
CSCD
北大核心
2019年第2期108-115,共8页
Pharmacology and Clinics of Chinese Materia Medica
基金
湖北省宜昌市科技局项目(A16-301-30)
