不同免疫抑制剂及甲泼尼龙对小鼠肺间质纤维化的疗效对比

Effects of immunosuppression drugs and prednisolone on mice model of bleomycin-induced pulmonary fibrosis

目的比较环磷酰胺、来氟米特和甲泼尼龙对博来霉素诱导的肺间质纤维化小鼠模型的疗效。方法将75只C57BL/6小鼠随机分成空白组、模型组、环磷酰胺组、来氟米特组及甲泼尼龙组(n=15)。空白组气管内注入0.9%氯化钠注射溶液0.2 m L,其余5组气管内注入博来霉素(5 mg/kg)建立肺纤维化模型,24 h后分别对空白组、模型组每日用0.2 m L 0.9%氯化钠注射溶液灌胃,药物组每日分别用环磷酰胺(50 mg/kg)、来氟米特(4 mg/kg)和甲泼尼龙灌胃(10 mg/kg)。并于造模后第7、14、28天分批处死小鼠,取小鼠肺脏评估肺泡炎程度及纤维化的程度。结果 (1)博来霉素诱导组小鼠体质量较对照组减轻(P<0.05),环磷酰胺、来氟米特组和甲泼尼龙组小鼠在第7、14、28天小鼠体质量较模型组均明显增加(P<0.05)。(2)与模型组相比,环磷酰胺组与甲泼尼龙组小鼠7天、14天时肺泡炎评分降低(P<0.05);第7天、14天、28天时纤维化评分明显降低(P<0.05)。而来氟米特组小鼠肺泡炎及纤维化评分较模型组差异无统计学意义。结论环磷酰胺和甲泼尼龙能显著降低博来霉素诱导的小鼠肺间质纤维化,减轻肺组织肺泡炎及肺纤维化程度,但来氟米特没有类似作用。

Objective To explore the effect of cyclophosphamide（CTX） ,leflunomide（LEF） and methylpred- nisolone（MP） on mouse model of bleomycin-induced pulmonary fibrosis. Methods A total of 75 C57BL / 6 mice were randomly and evenly divided into control group, model group, CTX group, LEF group and MP group （n = 15 in each group）. The mice in control group were injected 0.2 mL normal saline from endotracheal , and others were injected with O. 2mL bleomycin（5 mg/kg） from endotracheal to induce the pulmonary fibrosis model. The next day,the mice in con- trol group and model group were fed with 0.2mL normal saline every day;The mice in other groups were fed with respec- tively 0.2 mL CTX （50 mg/kg） ,0.2 mL LEF（4 mg/kg） and 0.2 mL MP （ 10 mg/kg） every day respectively. Finally the mice were sacrificed at day 7, day 14, day 28 separately, and the lung tissue was examined by HE staining and Mas- son staining to evaluate the degree of alveolitis and fibrosis. Results （ 1 ） The body mass of mice in bleomycin-induced groups were decreased compared with control group; （2） The pathological alveolitis scores in CTX group and MP group were significantly decreased compared with mode group at day 7 and day 14 （ P 〈 0.05 ）, and the pathological fibrosis scores were decreased dramatically compared with mode group at day 7, day 14 and day 28 （ P 〈 0.05 ）. While there was no statistical significance between LEF group and model group. Conclusions The CTX and MP can reduce and inhibit bleomycin-induced lung inflammation and fibrosis in mices, but not LEF.