慢性支气管炎小鼠模型构建方法的改良与评价

目的:结合慢性支气管炎的发病机制及致病因素,在以往单因素致病建模方法的基础上进行改良,探究一种较为准确、可靠、符合慢性支气管炎病理变化的模型。方法:慢支改良组(复合组)小鼠于实验第1、14天分别经气管和经鼻腔注入LPS,同时,于第2~30天(第14天除外)进行被动吸烟及SO2吸入;SO2组小鼠每天熏SO22 min;烟熏组小鼠每天吸烟4支/次,直至1包烟燃烧完毕,共约1 h;脂多糖组小鼠在造模第1天气管注入LPS,第14天、30天进行LPS滴鼻。各模型组均连续造模30 d。造模结束后通过对小鼠一般情况的观察、肺泡灌洗液结果分析以及支气管肺组织形态学观察等评价改良后的慢支模型。结果:造模后各模型组小鼠出现鼻部潮湿,咳嗽,体毛干枯无光泽,拱背蜷缩,少动,反应较为迟钝等症状,复合组的体质量增长最慢。从各组模型组病理切片可观察到细支气管壁周围有炎性细胞浸润,腔内炎性渗出明显,气道内分泌物增多等病变;与烟熏组、二氧化硫组比较,慢支改良组肺泡灌洗液白细胞总数显著增高(P0.01);慢支改良组与其它3组比较肺组织炎症细胞浸润程度显著升高(P0.01),且烟熏组与LPS组比较差异有统计学意义。结论:烟熏、二氧化硫、LPS均可导致小鼠慢支疾病的发生,而从支气管及肺组织病理学、肺泡灌洗液细胞学以及慢支的发病学等方面分析,复合因素造模更为符合慢支模型的构建。

Improvement and evaluation of chronic bronchitis modeling methods in mice

AIM: To explore a more accurate and reliable pathological model of the chronic bronchitis, which has improved from the former single-factor modeling method of the disease.METHODS: The mice in complex group were treated with lipopolysaccharide(LPS) by tracheal injection on the 1st day and nasal drops on the 14th day, and from the 2nd day to 30th day, the animals were given passive smoking and sulfur dioxide(SO₂) inhalation(except on the 14th day). The mice in SO₂ group were exposed to SO₂ 2 min per day, while in smoking group, the mice were exposed to smoke for about 1 h per day(4 cigarettes each time until one pack of cigarettes were burning up). In LPS group, the mice had tracheal injection of LPS on the 1st day and nasal drops of LPS on the 14th day and 30th day. Every modeling process lasted for 30 days. After modeling, the improvement of chronic bronchitis model was evaluated by testing the general conditions of the mice, analyzing leukocyte count in bronchoalveolar lavage fluid(BALF), and observing the morphological changes of the bronchial and lung tissues.RESULTS: After modeling, the mice in every model group experienced symptoms including wet nose, cough, dry and lusterless hair, arched back and curled-up body, showing inactive, and slow down in response. The mice in complex group gained the lowest weight compared to other groups. From each model group, the inflammatory cells infiltrated evidently around the bronchial walls, especially in the bronchial cavity, and the mucilage secretion in the airway increased. The total number of leukocytes in BALF increased significantly in complex group. The inflammatory cell count in the lung tissue indicated that the mice in complex group had significantly higher levels of inflammatory cell infiltration. Besides, the comparison between smoke group and LPS group was statistically significant.CONCLUSION: Smoking, SO₂ inhalation and LPS injection induce bronchial lung disease in mice, and the complex chronic bronchitis mouse model is a better model with the pathological changes of bronchus, lung tissue and BALF, and pathogenesis of chronic bronchitis.