【摘要】 目的 将大鼠IVC笼具手动气球挤压烟熏箱改装为生物隔离器内自动真空泵烟熏箱，建立稳定的烟气吸入微环境和解决实验过程中的生物安全隐患问题，以期进一步完善BALB/c小鼠慢性阻塞性肺疾病（chronic obstructive pulmonary disease,COPD）模型的制备。方法 选择SPF级雌性BALB/c小鼠72只，随机分为空白对照组12只、传统烟熏组30只和改良烟熏组30只。空白对照组不进行烟熏处理，传统烟熏组采用手动气球挤压吸入香烟烟雾，改良烟熏组采用吸入性疾病动物模型制备隔离器内微型真空泵吸入香烟烟雾，造模12周。观察BALB/c小鼠的一般情况，采用小动物呼吸机测定肺功能[肺动态顺应性（Cdyn）、功能残气量（FRC）、最大呼气量（FVC）、气道阻力（RI）]和病理学HE染色，评估改良实验动物烟气吸入微环境系统制备小鼠COPD模型的效果。结果 空白对照组BALB/c小鼠眼睛有神、活泼好动、毛发光泽、食欲正常、呼吸平稳及体重稳定增加；烟熏组BALB/c小鼠眼睛无神、活动减少、毛发干枯发黄、饮食减少、精神萎靡、弓背卷缩、呼吸急促、喘息及体重增长缓慢甚至减小，且改良组较传统组一般状态略差。与空白对照组比较，烟熏组BALB/c小鼠肺功能Cdyn增加，FRC减少，FVC减少及RI增大，且改良组较传统组明显，差异均有统计学意义（P<0.05）。HE染色显示，空白对照组BALB/c小鼠肺泡结构、肺内小支气管、血管均正常；烟熏组可见肺泡融合扩张、肺泡壁破损、肺内小支气管上皮脱落、肌层平滑肌增厚和血管壁增厚，且改良组较传统组明显。与空白对照组比较，BALB/c小鼠肺组织平均肺泡数（MAN）降低，肺泡平均截距（MLI）升高，且改良组较传统组明显，差异均有统计学意义（P<0.05）。结论 两组烟熏组均能制备小鼠COPD模型，但改良烟熏组制备的小鼠COPD模型肺功能改变更明显，且生物安全隔离器的使用解决了实验过程中的生物安全隐患问题。提示实验动物烟气吸入微环境系统的改良值得推广。更多还原

【Abstract】 Objective To improve the manual balloon compression smoking box of rat IVC cage into an automatic vacuum pump smoking box inside a biological isolator,establish a stable smoke inhalation microenvironment,and solve the biological safety hazards during the experiment,in order to further improve the preparation of the BALB/c mouse chronic obstructive pulmonary disease(COPD) model. Method A total of 72 SPF female BALB/c mice were randomly divided into the blank control group(12 rats),traditional smoking group(30 rats) and improved smoking group(30 rats). The blank control group was not smoked,the traditional smoking group was inhaled by manual balloon extrusion,and the improved fumigation group was inhaled by a miniature vacuum pump in an isolator prepared by an animal model of inhalation disease for 12 weeks. By observing the general information of BALB/c mice and the lung function [dynamic lung compliance(Cdyn),functional residual volume(FRC),maximum expiratory volume(FVC),airway resistance(RI)] by small animal ventilator and pathological examination,the effect of improving the smoke inhalation microenvironment system of experimental animals to prepare mouse COPD model was evaluated. Result The blank control group BALB/c mice had lively and active eyes,shiny hair,normal appetite,stable breathing,and stable weight gain. The BALB/c mice in the fumigation group had dull eyes,decreased activity,dry and yellow hair,reduced diet,mental depression,hunched back,Tachypnea,wheezing and slow or even decreased weight growth,and the general state of the improved group was slightly worse than that of the manual group. Compared with the blank control group,the smoking group showed an increase in lung function Cdyn,a decrease in FRC,a decrease in FVC,and an increase in RI in BALB/c mice,and the improved group showed significant differences compared to the manual group(P<0.05).BALB/c mice in HE staining blank control group could see normal alveolar structure,bronchiole and blood vessels in the lungs.In the fumigation group,alveolar fusion dilatation,alveolar wall damage,bronchiole epithelial shedding,muscle layer smooth muscle thickening and vascular wall thickening were observed,and the improved group was more obvious than the manual group;Compared with the blank control group,BALB/c mice showed a significant decrease in mean alveolar number(MAN) and an increase in mean alveolar intercept(MLI) in lung tissue,and the improved group showed significant differences compared to the manual group(P<0.05). Conclusion Both smoking groups can prepare mouse COPD models,but the lung function of the mouse COPD model prepared in the improved smoking group changes more significantly and is more consistent with the pathological changes of human COPD,and the use of biosafety isolators solves the problem of biosafety hazards in the experiment process,conforms to the biosafety law and the ethics of experimental Animal welfare,and the improvement of the smoke inhalation microenvironment system of experimental animals is worthy of wide promotion in the field of medical research.更多还原