当归补血汤调节自噬干预心肌梗死模型大鼠心肌损伤的作用机制  

Mechanism of Action of Danggui Buxue Decoction in Intervention Against Myocardial Injury by Regulating Autophagy in a Rat Model of Myocardial Infarction

作　　者：陈前 申楚翘 程凯 袁慧伦 叶树[1] 申国明[1] 江爱娟[1] CHEN Qian;SHEN Chuqiao;CHENG Kai;YUAN Huilun;YE Shu;SHEN Guoming;JIANG Aijuan(School of Integrated Traditional Chinese and Western Medicine,Anhui University of Chinese Medicine,Anhui Hefei 230012,China;Department of Pharmacy,The First Affiliated Hospital of Anhui University of Chinese Medicine,Anhui Hefei 230031,China)

机构地区：[1]安徽中医药大学中西医结合学院,安徽合肥230012 [2]安徽中医药大学第一附属医院药学部,安徽合肥230031

出　　处：《安徽中医药大学学报》2023年第1期92-97,共6页Journal of Anhui University of Chinese Medicine

基　　金：国家自然科学基金项目(81904147)。

摘　　要：目的观察当归补血汤对心肌梗死模型大鼠心肌损伤的影响并探究其作用机制。方法将大鼠随机分为假手术组,模型组,当归补血汤低、高剂量组和地尔硫[艹卓]组。连续给药7 d后结扎大鼠冠状动脉左前降支复制心肌梗死模型。缺血24 h后,采用TTC染色检测心肌梗死面积,苏木精-伊红染色检测心肌的组织形态,微板法检测乳酸脱氢酶(lactate dehydrogenase,LDH)水平,ELISA法检测肌酸激酶心肌型同工酶(creatine kinase-myocardial band,CK-MB)水平,Western blot法检测磷酸化磷脂酰肌醇3-激酶(phosphorylate phosphatidylinositol 3-kinase,p-PI3K),磷酸化蛋白激酶B(phosphorylate protein kinase B,p-AKT),磷酸化雷帕霉素靶蛋白(phosphorylate mammalian target of rapamycin,p-mTOR)及自噬相关蛋白LC3Ⅱ/Ⅰ、Beclin-1及p62蛋白的表达水平。结果当归补血汤能明显减少心肌梗死面积(P<0.05),降低血清CK-MB、LDH水平(P<0.05),减轻心肌组织的病理损伤,对心肌梗死具有明显的保护作用;Western blot结果显示,当归补血汤能降低自噬通路相关蛋白p-PI3K、p-AKT及p-mTOR的表达水平(P<0.05),升高自噬相关蛋白LC3Ⅱ/Ⅰ、Beclin-1的表达水平(P<0.05),降低p62的表达水平(P<0.05)。结论当归补血汤可能通过抑制PI3K/AKT/mTOR信号通路,激活自噬,改善心肌梗死模型大鼠的心肌损伤。Objective To investigate the effect of Danggui Buxue Decoction on myocardial injury and its mechanism of action in a rat model of myocardial infarction.Methods Rats were randomly divided into sham-operation group,model group,low-and high-dose Danggui Buxue Decoction groups,and diltiazem group.Ligation of the left anterior descending coronary artery was performed to establish a rat model of myocardial infarction after administration for 7 consecutive days.After 24 hours of ischemia,TTC staining was used to measure myocardial infarct area;HE staining was used to observe the histomorphology of myocardium;the microplate method was used to measure the content of lactate dehydrogenase(LDH);ELISA was used to measure the content of creatine kinase-MB(CK-MB);Western blot was used to measure the expression levels of phosphorylated phosphatidylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-AKT),phosphorylated mammalian target of rapamycin(p-mTOR),and the autophagy-related proteins LC3Ⅱ/Ⅰ,Beclin-1,and p62.Results Danggui Buxue Decoction significantly reduced myocardial infarct area(P<0.05),reduced the serum levels of CK-MB and LDH(P<0.05),and alleviated the pathological injury of myocardial tissue,suggesting that Danggui Buxue Decoction had a marked protective effect against myocardial infarction.Western blot showed that Danggui Buxue Decoction significantly reduced the expression levels of the autophagy pathway-related proteins p-PI3K,p-AKT,and p-mTOR(P<0.05),increased the expression levels of the autophagy-related proteins LC3Ⅱ/Ⅰ and Beclin-1(P<0.05),and reduced the expression level of p62(P<0.05).Conclusion Danggui Buxue Decoction may improve myocardial injury in the rat model of myocardial infarction by inhibiting the PI3K/AKT/mTOR signaling pathway and activating autophagy.

关 键 词：当归补血汤 心肌梗死 自噬 信号通路 PI3K AKT MTOR 

分 类 号：R542.22[医药卫生—心血管疾病] R285.5[医药卫生—内科学]