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中国应用生理学杂志 ›› 2022, Vol. 38 ›› Issue (5): 475-479.doi: 10.12047/j.cjap.6296.2022.089

• 研究论文 • 上一篇    下一篇

cAMP/Epac信号通路在当归治疗阴虚证慢性咳嗽中的作用*

杜玥, 王志旺, 席建宏, 李济阳, 梁可克, 黄柯婷, 罗慧英   

  1. 甘肃中医药大学, 兰州 730000
  • 收稿日期:2022-03-09 修回日期:2022-08-15 出版日期:2022-09-28 发布日期:2023-04-23
  • 通讯作者: Tel: 0931-8765395, 18919314848; E-mail: wzw0933@126.com, louria@163.com
  • 基金资助:
    *国家自然科学基金项目(81460668); 甘肃省自然科学基金项目(20JR5RA183, 1606RJZA011, 1310RJZA086); 2022年度甘肃省优秀研究生“创新之星”项目(2022CXZX-760);2022年度甘肃省优秀研究生创新之星项目(2022CXZX-762);甘肃中医药大学科学研究与创新基金项目(2022KCZD-4)

Effects of Angelicae Sinensis Radix on cAMP/Epac signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome

DU Yue, WANG Zhi-wang, XI Jian-hong, LI Ji-yang, LIANG Ke-ke, HUANG Ke-ting, LUO Hui-ying   

  1. Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
  • Received:2022-03-09 Revised:2022-08-15 Online:2022-09-28 Published:2023-04-23

摘要: 目的: 研究当归对阴虚证慢性咳嗽小鼠的治疗作用,以及对环磷酸腺苷(cAMP)/cAMP直接激活的交换蛋白分子(Epac)信号通路的影响。方法: 将小鼠随机分为空白对照组、模型对照组、阳性对照组及当归组(n=8),采用烟熏(每日1次,30 d)、内毒素滴鼻(0.4 mg/ml,每次10 μl,持续10次)、灌胃甲状腺(120 mg/kg,每日1次,持续15 d)并吸入氨水(每次3 min,持续10次)来复制阴虚证高反应性气道慢性感染咳嗽小鼠模型。在观察进食饮水、体重及自主活动的基础上,检测当归止咳对支气管肺泡灌洗液(BALF)中细胞因子、脑组织5-HT、肺组织相关活性因子(SP、PGP9.5、cAMP、Epac1)的影响。结果: 与模型对照组比较,当归组小鼠咳嗽次数明显减少,小支气管病理学变化明显缓解,BALF中IL-4、IL-13、TNF-α的含量明显降低,肺组织SP、PGP9.5以及cAMP、Epac1及其基因表达水平明显下调,脑组织5-HT的含量明显提高,同时可缓解饮水及进食量增加、自主活动增加等阴虚证表征指标(P<0.05, P<0.01)。结论: 当归具有一定的止咳作用,下调cAMP/Epac信号通路而缓解气道神经源性炎症、抑制咳嗽神经通路增敏是其作用机制之一。

关键词: 当归, 慢性咳嗽, 气道神经源性炎症, 咳嗽神经通路增敏, cAMP/Epac信号通路, 小鼠

Abstract: Objective: To investigate the effects of Angelicae Sinensis Radix (ASR) on cyclic adenosine monophosphate (cAMP) /exchange protein activated by cAMP (Epac) signaling pathway in the treatment of chronically infected cough mice with Yin deficiency syndrome. Methods: Mice were randomly divided into blank control group, model control group, positive control group and ASR group (n=8). The chronic cough mouse model of hyperreactive and infected airway with Yin deficiency syndrome was established with fumigation (once a day, 30 days in total), lipopolysaccharide nasal drip (every 3 days 10 μl, 10 times in total), intragastric administration of thyroid gland (120 mg/kg, once a day, a total of 15 days) and inhalation of ammonia (3 min / time × 10 times). On the basis of observing eating and drinking water, body weight and autonomic activities, the effects of ASR on metabolic level, autonomous activities, antitussive effect, cell factor in bronchoalveolar lavage fluid (BALF) brain tissue 5-HT and lung tissue related active factors(SP, PGP9.5, cAMP, Epac1) were detected. Results: ASR could significantly restrain cough, alleviate the pathological changes of bronchioles, reduce the contents of IL-4, IL-13, TNF-α in BALF and the levels of SP, PGP9.5, cAMP and Epac1 in lung tissues, increase the content of 5-HT in brain tissue (P<0.05, 0.01). Conclusion: ASR has some effects on restraining cough and one of its mechanisms is to down-regulate cAMP/Epac signaling pathway, to alleviate airway neurogenic inflammation and reduce sensitivity of cough neural pathway.

Key words: Angelicae Sinensis Radix (ASR), chronic cough, airway neurogenic inflammation, sensitivity of cough neural pathway, cAMP/Epac signal path, mice

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