艾拉莫德对博来霉素诱导的肺间质纤维化小鼠模型的影响

Effects of iguratimod on mice model of bleomycin-induced pulmonary fibrosis

目的 研究不同浓度艾拉莫德对博来霉素诱导的肺间质纤维化小鼠模型的影响.方法 将108只C57BL/6小鼠按随机数字表法分成对照组,模型组,艾拉莫德低剂量组、中剂量组、高剂量组及甲泼尼龙组（每组18只）.对照组气管内注入0.9％氯化钠注射液0.2 ml,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后分别对对照组、模型组每日用0.2 ml 0.9％氯化钠注射液灌胃,药物组每日分别用不同剂量艾拉莫德（10、30、90 mg/kg）和甲泼尼龙灌胃（10mg/kg）.并于造模后第7、14、28天分批处死小鼠,取小鼠肺脏采用苏木精-伊红（HE）染色及Masson染色的方法评估肺泡炎程度及纤维化的程度.统计学方法采用重复测量资料的方差分析,组间比较采用多因素方差分析的LSD检验.结果 ①所有博来霉素诱导组小鼠体质量较对照组均减轻（P〈0.05）,而艾拉莫德高剂量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,艾拉莫德高剂量组与甲泼尼龙组小鼠第7、14天时肺泡炎评分降低（P〈0.05）;第14 d、28天时纤维化评分明显降低（P〈0.05）.结论 艾拉莫德高剂量和甲泼尼龙对博来霉素诱导的小鼠肺纤维化模型的肺泡炎和肺纤维化有抑制作用.

Objective To explore the effect of different concentrations of iguratimod （IGU） on mouse model of bleomycin-induced pulmonary fibrosis.Methods A total of 108 female C57BL/6 mice were randomly divided into the control group,the model group,the low dose IGU group,the moderate dose IGU group,high dose with group and the methylprednisolone （MP） group （n=18 in each group）.The mice in the control group were injected with 0.2 ml normal saline endotracheally,and others were injected with 0.2 ml bleomycin （5 mg/kg） from endotracheally to induce pulmonary fibrosis model.The next day,the mice in both control group and the model group were fed with 0.2 ml normal saline every day;The mice in the IGU groups and methylprednisolone group were fed with 0.2 ml iguratimod liquid the IGU （10,30,90 mg/kg） and 0.2 ml methylprednisolone （10 mg/kg） every dayrespectively.Finally the mice were sacrificed at day 7,day 14,day 28 respectively,and the lung tissue was examined by HE staining and Masson staining to evaluate the degree of alveolitis and fibrosis.Repeated measurement of variance analysis was used to compare the differences for time and group,and multi-factor analysis of variance LSD test was used for the comparison between groups.Results ① The body mass of mice in bleomycin-induced groups were decreased compared to the control group.② The pathological alveolitis scores in the high dose IGU group and methylprednisolone group were significantly decreased compared to those of the model IGU group at day 7 and day 14 （P〈0.05）,and the pathological fibrosis scores were decreased dramatically compared with the model group at day 14 and day 28 （P〈0.05）.Conclusion High concentration of IGU and methylprednisolone can reduce and inhibit lung inflammation and fibrosis of bleomycin-induced pulmonary fibrosis in mice.