主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2020, Vol. 43 ›› Issue (4): 296-303.doi: 10.3969/j.issn.1006-2157.2020.04.006

• 中药药理 • 上一篇    下一篇

基于AKT/mTOR信号通路探讨复方七芍降压片治疗自发性高血压大鼠的作用机制

李弘1,刘叶倩1,龚姗1,刘林1,曾勇1,蔡晓1,王宇红2,任卫琼1#   

  1. 1 湖南中医药大学第一附属医院 湖南 410007;
    2 湖南中医药大学科技创新中心
  • 收稿日期:2019-10-11 出版日期:2020-04-30 发布日期:2020-05-14
  • 通讯作者: 任卫琼,女,硕士,副主任药师,硕士生导师,研究方向:中医药防治心血管疾病,E-mail:renweiqiong1@126.com
  • 作者简介:李弘,男,在读硕士生
  • 基金资助:
    国家自然科学基金资助项目(No.81473616),湖南省科技厅项目(No.2018SK51203),湖南省中医药管理局重点项目(No.201910),中医内科重大疾病防治及转化教育部重点实验室开放基金(No.ZYNK201703),研究生校级创新课题(No.2018CX37)

Mechanism of Compound Qishao Jiangya tablets in the treatment of spontaneously hypertensive rats based on AKT/mTOR signal pathway*

Li Hong1, Liu Yeqian1, Gong Shan1, Liu Lin1, Zeng Yong1, Cai Xiao1, Wang Yuhong2, Ren Weiqiong1#   

  1. 1 The First Hospital of Hunan University of Chinese Medicine, Hunan 410007 China;
    2 Institute of Innovation and Applied Research, Hunan University of Chinese Medicine, Hunan 410208,China
  • Received:2019-10-11 Online:2020-04-30 Published:2020-05-14
  • Contact: Ren Weiqiong, Deputy Chief Pharmacist. The First Hospital of Hunan University of Chinese Medicine. No.95 Shaoshan Middle Road,Yuhua District, Changshan 410007. E-mail:renweiqiong1@126.com
  • Supported by:
    National Natural Science Fund (No.81473616); Hunan Science and Technology Department Project (No.2018SK51203); Key Projects of Hunan Provincial Administration of Traditional Chinese Medicine (No.201910); Open Fund for Key Laboratories of the Ministry of Education for the Prevention and Transformation of Major Diseases in the Department of Internal Medicine (No.ZYNK201703)

摘要: 目的 探讨复方七芍降压片通过调控蛋白激酶B(AKT)/雷帕霉素靶蛋白(mTOR)信号通路对自发性高血压(SHR)大鼠血压、炎症因子及胸主动脉自噬相关蛋白表达的影响。方法 SHR大鼠30只,随机分为模型组、厄贝沙坦片组(27 mg/kg)、复方七芍降压片组(1.73 g/kg),连续给药6周,另设10只WKY大鼠为正常组,灌胃生理盐水。分别在给药前及给药1、2、3、4、5、6周,测量各组大鼠尾动脉血压。给药6周后取材,电镜观察胸主动脉超微结构及自噬情况;ELISA法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)水平;免疫组化法检测胸主动脉中Beclin-1、Bcl-2、AKT、mTOR蛋白表达;Western-blot检测胸主动脉中Beclin-1、Bcl-2蛋白表达。结果 与正常组比较,模型组大鼠血清IL-1β、IL-6水平升高(P<0.01);胸主动脉Bcl-2、AKT、mTOR蛋白表达升高(P<0.01或P<0.05),Beclin-1表达降低(P<0.01),且未见明显的自噬体结构。与模型组比较,复方七芍降压片组大鼠各周血压均降低(P<0.01);血清IL-1β、IL-6水平降低(P<0.05);胸主动脉中AKT、mTOR蛋白表达均降低(P<0.05),Beclin-1表达升高(P<0.05),且可见明显的自噬体结构。结论 复方七芍降压片能够降低SHR大鼠血压,其机制可能与抑制胸主动脉中自噬相关信号通路蛋白AKT、mTOR的表达,促进主动脉自噬,改善炎症反应有关。

关键词: 调控蛋白激酶/雷帕霉素靶蛋白信号通路, 自噬, 炎症反应, 复方七芍降压片, 自发性高血压大鼠

Abstract: Objective To investigate the effects of compound Qishao Jiangya tablet on blood pressure, inflammation factors and expression of aortic autophagy related proteins in spontaneously hypertensive (SHR) rats by regulating protein kinase B(AKT)/rapamicin target protein (mTOR) signaling pathway. Methods Thirty male SHR rats were randomly divided into model group, irbesartan group (27 mg/kg), and compound Qishao Jiangya tablet group (1.73 g/kg). Another 10 male WKY rats were used as normal control group (saline). All intervention was administered for 6 continuous weeks. The blood pressure of tail artery was measured by using noninvasive sphygmomanometer before treatment and at each week (W1-6) after treatment; Ultrastructure and autophagy of thoracic aorta was observed under electron microscope. Serum IL-1β and IL-6 levels was measured with ELISA. Beclin-1, Bcl-2, AKT, and mTOR protein expression in the thoracic aorta were evaluated by using immunohistochemical method while Beclin-1, Bcl-2 protein expression was measured with Weston Blot Assay. Results Compared with normal group, in the model group, serum IL-1β and IL-6 levels increased (P<0.01); the expression of Bcl-2, AKT, mTOR protein in thoracic aorta increased (P<0.01 or P<0.05), while the expression of Beclin-1 protein decreased (P<0.05). There was no apparent autophagosome structure. Compared with model group, the blood pressure of rats in the compound Qishao Jiangya tablet group decreased at every week (P<0.01). Serum IL-1β and IL-6 levels decreased (P<0.05). the expression of AKT and mTOR protein in the thoracic aorta decreased (P<0.05) while the expression of Beclin-1 protein increased (P<0.05). Autophagosome structure was present. Conclusion Compound Qishao Jiangya tablet can reduce blood pressure in SHR rats, and its mechanism may be related to inhibiting the expression of autophagy related signaling pathway protein AKT, mTOR in the thoracic aorta, promoting vascular autophagy and improving inflammatory response.

Key words: protein kinase B/rapamycin target protein, autophagy, inflammatory reaction, hypotension, Compound Qishao Jiangya tablet, spontaneously hypertensive rats

中图分类号: 

  • R285.5