COPD伴抑郁障碍小鼠模型的建立及加味温胆汤的干预作用

目的?建立一种烟熏诱导的小鼠慢性阻塞性肺疾病（COPD）伴抑郁障碍模型，并评价加味温胆汤对COPD伴抑郁障碍小鼠的治疗作用及其机制。方法?将小鼠随机分为正常组与模型组，模型组每天烟熏4次。烟熏满15周后，测试正常组与模型组糖水消耗，观察二者气道和肺组织的病理改变等，在确认COPD伴抑郁障碍小鼠模型成功后，将模型组小鼠随机分为模型组、加味温胆汤高剂量组、加味温胆汤低剂量组及阳性药组，连续给药3周，给药结束后，测试各组小鼠的糖水消耗、悬尾不动时间，检测肺功能，并检测小鼠支气管肺泡灌洗液（BALF）中炎症细胞数，观察气道和肺组织病理改变等。结果?与正常组相比，模型组小鼠在烟熏满15周时，体质量下降，糖水消耗比例降低，增强呼吸间歇（Penh）升高。连续给药3周后，与模型组相比，加味温胆汤组小鼠体质量增加，糖水消耗升高，悬尾不动时间减少，说明其抑郁样症状减轻；显著降低模型组小鼠吸气阻力（RI），升高肺动态顺应性（Cdyn）；显著降低总白细胞数与中性粒细胞数；降低肺泡灌洗液以及海马组织中炎症因子等。结论?用烟熏法所建立的COPD伴抑郁障碍小鼠模型较为符合本病的病程发展及临床特征，中药复方加味温胆汤对COPD伴抑郁障碍小鼠具有疗效，能够改善其病理与功能的改变，其机制可能与降低外周及中枢炎症有关。 

Establishment of Mice Model of COPD with Depression and Intervention Effects of Modified Wendan Decoction

OBJECTIVE?To establish the mice model of chronic obstructive pulmonary disease (COPD) complicated with depression induced by smoke， and to evaluate the therapeutic effects and mechanism of modified Wendan Decoction on these mice models. METHODS?Mice were randomly divided into normal control group and model group. Model group was given smoke four times a day. After 15 weeks， sugar consumption of both the model group and the control group were tested as well as the pathological changes of airway and lung tissue of the two groups were observed. In recognition of COPD with depression models being successfully constructed， mice in the model group were further randomly divided into model group， high dose group of Modified Wendan Decoction， low dose group of Modified Wendan Decoction and positive drug group， with the medicine administration lasting for 3 weeks. Then the sugar consumption， tail suspension test， pulmonary function and the number of inflammatory cells in bronchoalveolar lavage fluid (BALF) of each group were tested and the airway and lung tissue pathological changes were once more observed. RESULTS?Compared with normal control group， the weight and sugar consumption of model group decreased and the enhanced respiratory pause (Penh) increased after 15 weeks of smoking. Compared with the model group， the body weight and sugar consumption of the Modified Wendan Decoction group increased， with significantly reduced inspiratory resistance (RI)， increased lung dynamic compliance (Cdyn)， decreased total number of leukocyte and neutrophils than those of the model group. In addition， the bronchoalveolar lavage fluid and inflammatory factors in hippocampus were decreased. CONCLUSION?The COPD with depression mouse model established by smoke is in accordance with the disease development and and its clinical features. Chinese medicine Modified Wendan Decoction has therapeutic effects on the improvement of pathological and functional changes in mice with COPD and depression.