百草枯反复小剂量腹腔给药诱导小鼠肺纤维化模型

Lung fibrosis model made by repeated low - dose of paraquat administered intraperitoneally in mice

目的建立百草枯（PQ）诱导肺损伤及肺纤维化小鼠动物模型，并比较其与博莱霉素（BLM）的成模差异，进而建立一个更理想的动物模型。方法采用8～10周龄雄性C57BIM6J（C57）小鼠（n=30），随机（随机数字）分为百草枯腹腔给药组（n=10），博莱霉素气管给药组（n=10）及阴性对照组（n=10），PQ组经腹腔注射PQ10mg／kg，每3d一次，共5次，BLM组气管内注射BLM3mg／kg。分别于第7，14，21天处死小鼠，监测小鼠一般情况、体质量及肺组织病理改变。数据收集后采用SPSS13．0统计软件进行分析，两组之间的比较采用Mann-WhitneyU检验。结果PQ腹腔注射及气管注射BLM给药，都能造成肺损伤及纤维化模型。通过比较生存率、体质量变化、肺组织病理学的变化、成模率等指标，显示反复小剂量腹腔注射PQ较传统的BLM气管内注射的方法造模更方便有效，成功率更高。结论通过小鼠肺损伤及肺纤维化动物造模方法的比较，反复小剂量腹腔注射PQ为更理想的造模方式，并且较BLM诱导的方法有更高的成功率。

Objective To study the differences between the animal model of pulmonary injury/ fibrosis induced by using paraquat and that induced by using bleomycin in mice in order to establish an ideal mouse pulmonary fibrosis model. Methods Thirty healthy and 8 - 10 weeks old male C57BL/6J （ C57 ） mice were randomly （random number） divided into paraquat group （n = 10） , bleomycin group （n = 10）, and control group （ n = 10）. Paraquat （ 10 mg/kg） was given to mice intraperitoneally once every three days for 5 times in paraquat group. Bleomycin was injected into trachea of mice in a dose of 3 mg /kg in bleomycin group. The mice were sacrificed 7 days, 14 days and 21 days after administration of drug. The general physical condition, body weight and pulmonary pathological changes were observed . Data were analyzed with SPSS13.0 statistical package. The comparison was made between two groups with mann - whitney U-test. Results Both agents could induce pulmonary injury and fibrosis. After comparison of survival rate, body weight, pulmonary histopathological change and rate of successful modelling, the repeated low- dose of paraquat injected intraperitoneally was proved to be a method of more simple and effective with high success rate of modeling in comparison with the conventional technique of intratracheal injection of bleomycin. Conclusions By the comparison between two methods of establishing pulmonary injury and fibrosis models in mice , the method of repeated low - dose intraperitoneal injection of paraquat is superior over the bleomycin - induced method in respect of higher rate of successful modelling.