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

Abstract

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. 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. 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). 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.