银杏总黄酮抑制心肌细胞过度自噬对缺血性心力衰竭大鼠心肌重塑和内质网应激的调节  

Regulation of total flavone of ginkgo biloba on myocardial remodeling and endoplasmic reticulum stress in rats with ischemic heart failure by inhibiting excessive autophagy of cardiomyocytes

作　　者：刘永强[1] 刘辉[1,2] 韩培立[1] 周朝元[1] 崔勤涛[1] LIU Yong-Qiang;LIU Hui;HAN Pei-Li;ZHOU Chao-Yuan;CUI Qin-Tao(The First Affiliated Hospital of Xinxiang Medical University,Xinxiang 453100,China)

机构地区：[1]新乡医学院第一附属医院心外科,新乡453100 [2]新乡医学院第一附属医院心内科,新乡453100

出　　处：《中国免疫学杂志》2020年第12期1457-1461,共5页Chinese Journal of Immunology

基　　金：河南省医学科技攻关项目(No.201602155)资助。

摘　　要：目的:探究银杏总黄酮(TFG)抑制心肌细胞过度自噬对缺血性心力衰竭(IHF)大鼠心肌重塑和内质网应激(ERS)的调节作用。方法:左冠状动脉结扎法构建IHF大鼠模型,造模前给予TFG 25 mg/kg、100 mg/kg灌胃处理,连续7 d,1次/d,同时设立空白对照组(Control)和美托洛尔组[美托洛尔片12 mg/(kg·d)];HE染色观察大鼠心肌组织结构损伤,qRT-PCR和免疫组化检测心肌组织中Caspase-3含量,心脏超声心动图检查大鼠左心室射血分数(LVEF)、左室短轴缩短率(FS)、左室壁厚度(LVWT)、左心室收缩期末容积(LVESV)、左心室舒张末容积(LVEDV),Western blot检测ERS和自噬相关蛋白表达。结果:与IHF model组相比,给予TFG处理后心肌细胞排列趋于整齐,细胞间隙明显减少,LVWT、LVWF、FS、GADD34、Bip及p62表达明显升高,LVESV、LVEDV、Caspase-3、CHOP、cleaved Caspase-12、Beclin1、LC3Ⅱ/LC3Ⅰ水平明显下降(P<0.05),且高剂量组改善效果与阴性对照组相近,明显优于低剂量组(P<0.05)。结论:银杏总黄酮可有效抑制IHF大鼠心肌细胞的凋亡和心肌重塑,可能与内质网应激和自噬相关蛋白有关。Objective:To investigate regulating effects of total flavone of ginkgo biloba(TFG)on myocardial remodeling and endoplasmic reticulum stress(ERS)in rats with ischemic heart failure(IHF)by inhibiting excessive autophagy of cardiomyocytes.Methods:IHF rat models were constructed by left coronary artery ligation,which were given TFG gavage before modeling(25 mg/kg,100 mg/kg),continuous for 7 d,once a day.Blank control group(Control)and metoprolor group[Metoprolol table,12 mg/(kg·d)]were set up.HE staining was performed to observe damage of myocardial tissue structure in rats.qRT-PCR and immunohistochemistry were performed to detect content of Caspase-3 in myocardial tissues.Left ventricular ejection fraction(LVEF),left ventricular short axis fractional shortening(FS),left ventricular wall thickness(LVWT),left ventricular end systolic volume(LVESV)and left ventricular end diastolic volume(LVEDV)were examined by echocardiography.Western blot was performed to detect ERS and autophagy-related protein expressions.Results:Compared with IHF model group,arrangement of cardiomyocytes tended to be tidy after TFG treatment,intercellular space was significantly less.LVWT,LVWF,FS,GADD34,expressions of Bip and p62 were significantly increased,levels of LVESV,LVEDV,Caspase-3,CHOP,cleaved Caspase-12,Beclin1,LC3Ⅱ/LC3Ⅰwere significantly decreased(P<0.05).Improvement effect of high-dose group was similar to that of negative control group,significantly better than that of low-dose group(P<0.05).Conclusion:TFG can effectively inhibit cardiomyocyte apoptosis and myocardial remodeling in IHF rats,which may be related to ERS and autophagy-related proteins.

关 键 词：银杏总黄酮 缺血性心力衰竭 心肌重塑 内质网应激 自噬 

分 类 号：R258.5[医药卫生—中医内科学]