慢性应激所致焦虑/抑郁状态对哮喘小鼠气道炎性反应的影响

Effects of anxiety and depression status caused by chronic stress on airway inflammation in asthmatic mice

目的探讨慢性应激对哮喘炎症水平的影响以及抗抑郁药物对合并焦虑/抑郁的哮喘小鼠的治疗效果。方法将C57BL小鼠分为对照组(CTRL组)、哮喘组(OVA组)、应激组(CTRL/R组)、哮喘应激组(OVA/R组)、帕罗西汀组(CTRL/R+P组)、哮喘+帕罗西汀组(OVA/R+P组)。OVA、OVA/R、OVA/R+P组以OVA和Al2(OH)3混悬液腹腔内注射致敏,每7天1次,致敏21d后再以OVA激发液连续滴鼻7d制备经典哮喘模型。同时CTRL/R、OVA/R、CTRL/R+P组和OVA/R+P组采用慢性束缚应激的方式构建应激模型。CTRL/R+P组和OVA/R+P组小鼠束缚前30min予以帕罗西汀溶液腹腔注射。在第27天观察小鼠糖水偏好指数变化情况,检测其气道反应性。第28天称量小鼠体质量并分离双侧肾上腺称量湿重,收集肺泡灌洗液进行细胞分类计数,肺组织切片进行HE染色和PAS染色,评价小鼠肺部炎症及气道黏液分泌情况。结果与OVA组相比,OVA/R组小鼠体质量减轻,糖水偏好指数降低,肾上腺/体质量比值增高,并且气道高反应、气道炎症以及气道黏液高分泌表现均较OVA组小鼠加重;而在给予帕罗西汀治疗后,OVA/R+P组小鼠的气道高反应、气道炎症以及气道黏液高分泌较OVA/R组小鼠均有所缓解,体质量减轻程度及糖水偏好指数改善。结论慢性应激导致的小鼠焦虑/抑郁状态会明显加重哮喘小鼠气道炎症水平,使用帕罗西汀抗抑郁治疗后,哮喘小鼠气道炎症得到了有效缓解。

Objective To investigating the effects of chronic stress on the inflammatory level of asthma and the therapeutic effect of antidepressants on the asthmatic mice with complicating anxiety and depression. Methods The C57BL mice were divided into the control group(CTRL),asthma group(OVA),stress group(CTRL/R),asthma and stress group(OVA/R),paroxetine group(CTRL/R+P) and asthma+paroxetine group (OVA/R+P).The OVA,OVA/R and OVA/R+R groups were sensitized by peritoneal injection of OVA and Al 2(OH) 3 suspension,once every seven days,after sensitization for 21 d,continuous nose dropping was conducted by the OVA stimulating solution for preparing the asthma model.Meanwhile the CTRL/R,OVA/R,CTRL/R+P and OVA/R+P groups adopted the chronic constraint stress mode to construct the stress model.The CTRL/R+P group and OVA/R+P group were peritoneal injected by paroxetine solution at 30 min before restraint.The change of sucrose preference index was observed and the airway reactivity was measured on 27 d.The mouse body mass was weighed on 28 d and the bilateral adrenal glands were separated and the wet weight was weighed on 28 d.The bronchoalveolar lavage fluid(BALF) was collected for conducting the cell classification count.The lung tissue sections were stained with HE and PAS to evaluate the lung inflammation and airway mucus secretion in mice. Results Compared with the OVA group,the body mass in the OVA/R group was reduced,the sucrose preference index was decreased,the adrenal/body mass ratio was increased,moreover the manifestations of airway hyperresponsiveness,airway inflammation and airway mucus hypersecretion were more aggravated compared with the asthmatic mice.After paroxetine treatment,the airway hyperresponsiveness,airway inflammation and airway mucus hypersecretion in the OVA/R+P group were alleviated compared with the asthma stress group,body mass reduce degree and sucrose preference index were also improved. Conclusion Anxiety and depression caused by chronic stress aggravate the airway inflammation in asthmatic mice.After antidepressant therapy with paroxetine,the airway inflammation is effectively alleviated.