mTOR抑制剂对博来霉素诱导小鼠肺纤维化的作用研究

The Role of mTOR in the Treatment Bleomycin-induced Pulmonary Fibrosis at Mice

目的探讨mTOR抑制剂雷帕霉素在博来霉素(BLM)诱导的小鼠肺纤维化中的治疗效果。方法对60只C57BL/6小鼠行气管内滴注博来霉素诱导的肺纤维化模型。在纤维化模型前5天,每天连续腹腔注射雷帕霉素预处理5天。将小鼠随机分为两组:腹腔注射赋形剂的对照组和腹腔注射雷帕霉素的治疗组。在造模第21天取小鼠肺组织标本用Western blotting方法检测mTOR信号通路的变化;同时用HE和Masson染色分析肺组织形态学变化;运用Ashcroft评分及羧脯氨酸含量评估肺纤维化程度。结果雷帕霉素抑制了纤维化小鼠肺组织内mTOR的活化。赋形剂组与雷帕霉素治疗组的肺损伤程度和纤维化变化无差异。两组的Ashcroft评分和羧脯氨酸含量差异无统计学意义(P> 0.05)。结论 mTOR抑制剂雷帕霉素预处理未能缓解博来霉素诱导的小鼠肺纤维化病变。

Objective To investigate the role of mTOR inhibitor rapamycin in the treatment of bleomycin-induced pulmonary fibrosis at mice.Methods Sixty C57BL/6 mice were induced by single intratrachea instillation of bleomycin(2.5mg/kg).In order to establish pulmonary fibrosis model.Before 5 days of pulmonary fibrosis model,rapamycin was injected intraperitoneally for 5 consecutive days.All mice were randomly divided into two groups,control group and intraperitoneal injection rapamycin group.Then all mice were sacrificed at 21 days.The activity of mTOR signaling pathway was measured by Western blotting.Also,the lungs were collected for morphometric analysis with HE and Masson staining.The degree of pulmonary fibrosis was evaluated with Ashcroft score and hydroxyproline content.Results Rapamycin inhibited the activation of mTOR in lung tissue of fibrotic mice.There was no difference in the degree of lung injury and fibrosis between excipient group and rapamycin group.There was no significant difference in Ashcroft score and carboxyproline content between the two groups(P>0.05).Conclusion Pretreatment with rapamycin,a mTOR inhibitor,failed to alleviate bleomycin-induced pulmonary fibrosis in mice.