一种感染后咳嗽动物模型制作方法的建立及评价

Establishment and Evaluation for an Animal Model of Post-infectious Cough

目的:评价用小剂量内毒素(LPS)滴鼻诱导慢性吸入纸烟烟雾的大鼠,建立感染后咳嗽(PIC)动物模型的方法。方法:采用随机数字表法将50只SPF级雄性纯白SD大鼠分为空白组、感染后咳嗽模型A组、模型B组、模型C组、模型D组。首先迫使各模型组大鼠慢性吸入纸烟烟雾造成其气道高反应,然后分别用浓度为0.2mg/mL、0.4 mg/mL、0.6 mg/mL、1 mg/mL的LPS溶液滴鼻诱导大鼠气道炎症,最后用辣椒素刺激法创建PIC动物模型。观察大鼠行为变化及咳嗽性质,检测BALF中细胞分类计数,经TP-603T型传感器测定咳嗽反应性;HE染色观察肺组织病理变化。结果:①模型A组与B组大鼠咳嗽频发,且咳嗽动作较典型,其中模型B组更明显。②咳嗽反应性测定:各模型组与空白组相比5 min内咳嗽次数均有明显增加(P<0.001),但数据分析显示A组、B组更具有统计学差异。③模型A组与B组BALF中白细胞总数、巨噬细胞、中性粒细胞及淋巴细胞比率与空白组相比均有明显差异(P<0.05),其中B组差异更显著(P<0.01)。④病理结果显示模型A组与B组大鼠均出现气道炎症表现,尤以模型B组更为明显,而均未见明显的肺间质炎症和肺泡的融合。结论:用小剂量LPS滴鼻诱导慢性吸入纸烟烟雾的大鼠建立PIC动物模型的方法可使大鼠咳嗽反应性增高,并产生显著的气道炎症改变,而肺实质则无明显炎症表现。

Objective ：To evaluate the established rats models of post- infectious cough（PIC） with small doses of endotoxin （LPS） to induce chronic inhalation of cigarette smoke. Method： Using a random number table ,50 SPF male white SD rats were divided into blank group, PIC model group A, model B group, model group C, model D group. First each model rats were forced to have a chronic inhalation of cigarette smoke to cause airway hyperresponsiveness, and then 0.2 mg/ mL,0.4 mg,/mL,0.6 mg/mL, 1 mg/mLLPS solution was intranasaUy used to induce airway inflammation, and the last capsaicin stimulation was to create the animal model. The behavioral changes in rats and the nature of the cough was observed. The detection cell count in BALF and cough reactivity were measured by the TP -603T sensors. Lung histopathol- ogyl was evaluated by HE staining. Result ： ①Model group A and group B rats coughed frequently, and the movements of cough were more typical, and model group B was more obvious. ②Determination of cough reactive ： each model group compared with the control group ,5 rain cough had been increased significantly （P 〈 0.001 ）, but the data analysis showed that group A, group B had more significant difference. ③The model group A and group B were significantly different in BALF WBC,macrophages ,neutrophils and lymphocytes ratio compared with blank control group （P 〈 0. 05 ）; compared with group B differences were more significant （P 〈 0.01 ）. （~）Model group A and group B rats showed airway inflammation,it was more obvious in the model group B especially, while there was no significant pulmonary interstitial inflammation ahd alveolar fusion. Conclusion ： The method of establishing PIC animal model with small dose of LPS to induce chronic inhalation of cigarette smoke can make the increased reactivity, and produce significant changes in airway inflammation, while there is no significant inflammation of the lung parenchyma.