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。
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.
作者
李弘
刘叶倩
龚姗
刘林
曾勇
蔡晓
王宇红
任卫琼
Li Hong;Liu Yeqian;Gong Shan;Liu Lin;Zeng Yong;Cai Xiao;Wang Yuhong;Ren Weiqiong(The First Hospital of Hunan University of Chinese Medicine,Hunan 410007 China; Institute of Innovation and Applied Research,Hunan University of Chinese Medicine,Hunan 410208,China)
出处
《北京中医药大学学报》
CAS
CSCD
北大核心
2020年第4期296-303,共8页
Journal of Beijing University of Traditional Chinese Medicine
基金
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)。
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
protein kinase B/rapamycin target protein
autophagy
inflammatory reaction
hypotension
Compound Qishao Jiangya tablet
spontaneously hypertensive rats
作者简介
李弘,男,在读硕士生;通信作者: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。
