国际医药卫生导报 ›› 2023, Vol. 29 ›› Issue (6): 801-807.DOI: 10.3760/cma.j.issn.1007-1245.2023.06.013

• 论著 • 上一篇    下一篇

麝香保心丸通过SIRT1/mTOR信号通路参与兔急性心肌梗死血管再生的研究

魏景迅  董彬昌  杜鑫  徐会圃   

  1. 滨州医学院附属医院心血管内科,滨州 256603

  • 收稿日期:2022-09-06 出版日期:2023-03-15 发布日期:2023-04-02
  • 通讯作者: 徐会圃,Email:xuhuipu@126.com
  • 基金资助:

    滨州医学院科研计划(BY2017KJ16);中国中西医结合协会-科研基金项目(2018010

Effect of Shexiang Baoxin Pills on angiogenesis in rabbits with acute myocardial infarction through SIRT1/mTOR signaling pathway

Wei Jingxun, Dong Binchang, Du Xin, Xu Huipu   

  1. Department of Cardiovascular Medicine, Binzhou Medical University Hospital, Binzhou 256603, China

  • Received:2022-09-06 Online:2023-03-15 Published:2023-04-02
  • Contact: Xu Huipu, Email: xuhuipu@126.com
  • Supported by:

     Scientific Research Plan of Binzhou Medical University Hospital (BY2017KJ16); Project of Scientific Research Fund of Combined Chinese and Western Medicine Association in China (2018010)

摘要:

目的 探讨麝香保心丸通过SIRT1/mTOR信号通路参与兔急性心肌梗死(AMI)后血管再生的机制。方法 202110月至20223月进行实验,选择雄性新西兰大白兔,共40只,月龄23个月,体质量2.02.5 kg,通过丝线结扎新西兰大白兔左冠状动脉前降支构建兔急性心肌梗死模型,并记录肢体导联心电图判定造模成功。将兔分为对照组(麝香保心丸+正常兔组)、假手术组、生理盐水+AMI组、麝香保心丸+AMI组,每组10只,术后7 d处死动物并留取心肌组织。采用HE染色观察各组兔心肌组织学改变;苦味酸染色观察各组兔急性心肌梗死程度;免疫组化法检测各组心肌组织中血管内皮细胞生长因子(VEGF)、沉默信息调节因子1SIRT1)、自噬相关基因(Beclin1)、雷帕霉素靶蛋白(mTOR)的表达;免疫荧光标记CD31标记微血管密度(MVD),观察各组兔血管再生情况。统计学方法采用F检验。结果 生理盐水+AMI组及麝香保心丸+AMIVEGFBeclin1mTOR表达均高于对照组、假手术组,而SIRT1表达低于对照组、假手术组(F=47.47834.17940.90821.710,均P<0.05)。麝香保心丸+AMI组心肌梗死面积低于生理盐水+AMI组,差异有统计学意义(F=68.865P<0.05);麝香保心丸+AMICD31免疫荧光标记MVD高于生理盐水+AMI组,VEGFBeclin1mTORSIRT1阳性表达均高于生理盐水+AMI组。结论 急性心肌梗死发生后自噬增强,麝香保心丸在急性心肌梗死发生后可通过SIRT1/mTOR信号通路影响血管再生,从而抑制心室重塑及心功能下降。

关键词:

麝香保心丸, 急性心肌梗死, SIRT1, mTOR, 自噬, 血管再生

Abstract:

Objective To explore the mechanism of Shexiang Baoxin Pills (SBP) participating in angiogenesis after acute myocardial infarction through the SIRT1/mTOR signaling pathway. Methods The trial was from October 2021 to March 2022. Forty New Zealand male rabbits were selected; they were 2-3 months old; their body weight was 2.0-2.5 kg. The rabbit models of acute myocardial infarction were established by ligating the left anterior descending coronary arteries with silk thread. The limb lead ECG was recorded to determine the models' success. The rabbits were divided into a control group (SBP+ normal rabbit group), a sham operation group, a saline + AMI group, and an SBP + AMI group, with 10 in each group. The animals were sacrificed 7 days after the operation, and the myocardial tissue was collected. HE staining was used to observe the histological changes of rabbit myocardium in each group; the degree of acute myocardial infarction was observed by picric acid staining; the immunohistochemical method was used to detect the expression of vascular endothelial growth factor (VEGF), SIRT1, Beclin1, and mTOR protein in the myocardial tissue of each group; immunofluorescence CD31 labeled microvascular density (MVD) was used to observe the rabbits' vascular regeneration in each group. F test was applied. Results Compared with those in the control group and the sham operation group, the expressions of VEGF, Beclin1, and mTOR in the normal saline + AMI group and the SBP + AMI group were higher, while the expression of SIRT1 was lower (F=47.478, 34.179, 40.908, and 21.710; all P<0.05). Compared with that in the normal saline + AMI group, the myocardial infarction area in the SBP + AMI group was smaller, with a statistical difference (F=68.865, P<0.05); the CD31 immunofluorescence labeled MVD and the positive expressions of VEGF, Beclin1, mTOR, and SIRT1 in the SBP + AMI group were higher than those in the normal saline + AMI group. Conclusions Autophagy is enhanced after acute myocardial infarction; SBP can affect angiogenesis through the SIRT1/mTOR signaling pathway after acute myocardial infarction and inhibit ventricular remodeling and decline of cardiac function.

Key words:

Shexiang Baoxin Pills, Acute myocardial infarction, SIRT1, mTOR, Autophagy, Vascular regeneration