cAMP/Epac信号通路在当归治疗阴虚证慢性咳嗽中的作用  

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

作　　者：杜玥 王志旺[1] 席建宏 李济阳 梁可克 黄柯婷 罗慧英[1] DU Yue;WANG Zhi-wang;XI Jian-hong;LI Ji-yang;LIANG Ke-ke;HUANG Ke-ting;LUO Hui-ying(Gansu University of Traditional Chinese Medicine,Lanzhou 730000,China)

机构地区：[1]甘肃中医药大学,兰州730000

出　　处：《中国应用生理学杂志》2022年第5期475-479,496,共6页Chinese Journal of Applied Physiology

基　　金：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)。

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10μl,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。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 10μl,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-αin 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.

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 

分 类 号：R562.25[医药卫生—呼吸系统] R285.5[医药卫生—内科学]