Effects Of Anxiety And Depression Induced By Chronic Stress On Airway Inflammation In Asthmatic Mice

Objective:As a common chronic inflammatory disease of respiratory tract all over the world,airway inflammatory cell infiltration,mucus hypersecretion and airway remodeling are important pathological features of bronchial asthma.And anxiety disorder and depression are one of the common complications in bronchial asthma.In modern fast-paced work and life,a large number of people are in a state of psychological stress for a long time,some even developed into mental disorders,such as anxiety disorder and depression.Psychological stress has also been proved to play an important role in the occurrence and development of some diseases.But up to now,the effect of anxiety disorder or depression on bronchial asthma and its corresponding mechanism are not completely clear,and there is lack of related research on this aspect.The aim of this study is to explore the effect of chronic stress on the inflammatory level of asthma by constructing a mice model of asthma combined with chronic stress,and to further explore the effect of antidepressants on asthmatic mice with anxiety and depression.Methods:In this experiment,30 healthy female C57BL mice of SPF grade were selected by sucrose preference test before experiment and randomly divided into 6 groups?n=5?:control group?CTRL?,asthma group?OVA?,stress group?CTRL/R?,asthma stress group?OVA/R?,paroxetine group?CTRL/R+P?,asthma paroxetine group?OVA/R+P?.During the sensitization phase of asthma,mice in asthma group,asthma stress group and asthma paroxetine group were sensitized by intraperitoneal injection of Ovalbumin?OVA?and Aluminum hydroxide[Al₂?OH?₃]suspension in accordance with 0.2ml per mice every 7days,from the 21st day of sensitization,the classical asthma model was established by continuously nasal drip with 50?l of Ovalbumin?OVA,2mg/ml?provocation solution for 7 days.At the same time,mice in stress group,paroxetine group and asthma paroxetine group were used chronic restraint stress to preparation mice model of chronic stress.Mice in paroxetine group and asthma paroxetine group were intraperitoneally injected paroxetine solution?1mg/ml?30 minutes before restraint according to 10mg/kg body weight.On the 27th day,the changes of sucrose preference index in each group were observed and recorded,and the airway reactivity of mice stimulated by acetylcholine with different concentration gradient was measured by Buxco FinePointe whole body plethysmograph system.The Penh value curve was plotted according to the recorded results.After weighing the body weight of mice on the 28th day,all mice were killed by disconnection of the spinal cord and separated bilateral adrenal glands and weight their wet weight.Separated the muscles and fascia in front of the mice necks,fully exposed tracheae of the mice and ligated the proximal end of tracheae,1ml PBS precooled by 4?refrigerator was slowly injected through trachea with empty needle for alveolar lavage.After three times of repeated aspiration,the total bronchoalveolar lavage fluid?BALF?was collected for later centrifugation and resuspension.The cells in the lavage fluid were classified and counted and smear HE staining were performed.The left lung lobe of mice without lavage were embedded and cut into sections then stained with HE and PAS respectively,the lung inflammation and airway mucus secretion in mice were evaluated according to the pathological sections.Results:Asthma model and chronic restraint stress model of mice were successfully constructed in this experiment.?1?The mice showed decrease intake of sucrose and body weight lost after chronic restraint stress,and the stress also induced the hyperplasia of the adrenal gland by activating the HPA axis.As a result,the sucrose preference index decreased and the ratio of adrenal gland to body weight increased.Compared with asthma group mice,the body weight loss,sucrose preference index and adrenal gland/body weight ratio of asthma stress group mice were decreased,and the changes of body weight and sucrose preference index before and after the chronic stress were more obvious than those in asthma group and stress group mice.The adrenal gland/body weight ratio was the highest,which confirmed the successful construction of our animal model.After paroxetine treatment,the weight loss and the sucrose preference index of the mice were improved,and the adrenal gland/body weight ratio decreased.?2?After inhalation of acetylcholine,airway reactivity in asthma stress group was significantly increased,the airway inflammation and airway mucus hypersecretion were more serious than those mice in asthma group.However,after treated with paroxetine,the airway hyperresponsiveness,airway inflammation and airway mucus hypersecretion in the asthma paroxetine group were relieved than those in the asthma stress group mice.?3?The inflammatory cells in alveolar lavage fluid of asthma stress group mice were increased significantly,especially eosinophilic granulocyte and neutrophil.But the airway inflammation score and the inflammatory cell count in alveolar lavage fluid were decreased in asthma paroxetine group mice after paroxetine treated.Conclusion:Asthma model and chronic restraint stress model of C57BL mice were successfully constructed in this experiment.Anxiety and depression induced by chronic stress can aggravated airway hyperreactivity and promoted airway inflammation and airway mucus secretion in asthmatic mice.After antidepressant treatment with paroxetine,airway inflammation and airway mucus secretion were effectively alleviated in asthmatic mice,it also alleviated the airway hyperreactivity of mice to some extent.It provides a reference for the treatment of anti-anxiety and depression drugs in asthmatic patients suffering from anxiety and depression.