胆酸诱导急性肺损伤小鼠模型的建立和评价

Establishment and evaluation of a mouse model of acute lung injury induced by cholic acid

目的构建胆酸诱导急性肺损伤(ALI)的小鼠模型,筛选给药方式,探讨胆酸致肺损伤的可行性。方法按照给药方法×药物(3×3)析因设计分组小鼠,给药方法包括气管切开、鼻滴1 d和鼻滴6 d,药物为胆酸及其溶解对照DMSO和空白对照PBS,故共计9组小鼠。给药期间监测体重变化,给药结束后对胸部行X线平片检查、组织学观察肺组织的病理学变化、取动脉血分析血氧分压(PO2),ELISA法检测肺组织中肿瘤坏死因子(TNF-α)和白介素1β(IL-1β)的含量。结果气管切开再灌注胆酸组的X线平片呈现肺组织弥散性浸润,肺大体样本有明显的出血表现,组织学病理显示出大量的炎细胞浸润和肺泡壁增厚,血氧分压降低,TNF-α和IL-1β显著高于其它各组。鼻滴1 d胆酸组和鼻滴6 d胆酸组的各指标较变化不及气管切开再灌注胆酸组。结论气管切开并灌注胆酸可以成功构建小鼠急性肺损伤模型。

Objective To construct an acute lung injury mouse model induced by cholic acid with intratracheal instillation or intranasal infusion,and to screen the perfusion method and verify the feasibility of bile acid-induced lung injury.Methods Mice were grouped according to the factorial design of administration method×drug(3×3).The administration method included tracheotomy,nasal drops for 1 day,and nasal drops for 6 days.Animals were administered either cholic acid,DMSO,or PBS;in total,there were nine groups of mice.During the administration period,body weight changes were monitored.After administration,chest X-ray examination was performed,histological observation of the pathological changes of the lung tissue was carried out,arterial blood was taken to analyze the partial pressure of oxygen(PO2),and ELISA was used to detect tumor necrosis in the lung tissue,as demonstrated by tumor necrosis factor-α(TNF-α)and interleukin 1β(IL-1β)expression.Results The X-ray result of the intratracheal instillation and reperfusion cholic acid group showed diffuse infiltration of lung tissue.Gross lung samples showed obvious hemorrhage,while histopathology showed a large amount of inflammatory cell infiltration and alveolar wall thickening.Blood oxygen partial pressure was decreased,and TNF-αand IL-1βwere significantly higher than in the other groups.The indexes of the cholic acid group after 1 day of intranasal infusion and 6 days of intranasal infusion were not as good as those in the cholic acid group after intratracheal instillation and reperfusion.Conclusions The acute lung injury model can be successfully constructed by intratracheal instillation of cholic acid.