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目的研究肿瘤抑制素M(OSM)及其下游通路在吉非替尼干预的肺纤维化小鼠中的改变,探讨OSM及下游通路在肺纤维化中的作用。方法 36只SPF级昆明小鼠随机分为3组:正常组(生理盐水气管内雾化)、博莱霉素组(博莱霉素3 mg/kg气管内雾化)、吉非替尼处理组(博莱霉素气管内雾化后,每天吉非替尼20 mg/kg灌胃)。实验第14天收集肺标本,肺组织行HE与Masson染色;RT-PCR法检测α-SMA、OSM m RNA表达水平;Western blot法检测α-SMA、OSM、ERK1/2、P-ERK1/2、P38、P-P38蛋白表达水平。结果博莱霉素组小鼠肺组织病理损伤较正常组小鼠明显加重、胶原沉积明显增加、炎症损伤评分及纤维化评分明显增加(P<0.05),α-SMA、OSM m RNA及蛋白表达水平明显升高(P<0.05),p-ERK1/2、p-P38蛋白表达水平明显升高(P<0.05),吉非替尼组小鼠上述指标均较博莱霉素组明显降低(P<0.05)。结论吉非替尼能显著缓解博莱霉素诱导的小鼠肺纤维化,其机制可能与抑制OSM m RNA及蛋白的表达及其下游P38和ERK1/2的磷酸化密切相关。
Objective To investigate the changes of tumor suppressor M (OSM) and its downstream pathways in mice with pulmonary fibrosis induced by gefitinib and explore the role of OSM and downstream pathways in pulmonary fibrosis. Methods Thirty-six SPF Kunming mice were randomly divided into three groups: normal group (normal saline intratracheal instillation), bleomycin group (bleomycin 3 mg / kg intratracheal nebulization), gefitinib treatment Group (Bleomycin intratracheal nebulization, daily gefitinib 20 mg / kg gavage). The lung specimens were collected on the 14th day of the experiment and the lung tissues were stained with HE and Masson. The expressions of α-SMA and OSM mRNA were detected by RT-PCR. The expressions of α-SMA, OSM, ERK1 / 2 and P-ERK1 / 2 , P38, P-P38 protein expression levels. Results The pathological changes of lung tissue in bleomycin group were significantly more than those in normal group. Collagen deposition, inflammatory injury score and fibrosis score were significantly increased (P <0.05), α-SMA, OSM m RNA and protein expression (P <0.05). The expression of p-ERK1 / 2 and p-P38 protein in the gefitinib group was significantly lower than that in the bleomycin group (P <0.05) P <0.05). Conclusion Gefitinib can significantly attenuate bleomycin-induced pulmonary fibrosis in mice. The mechanism may be related to inhibition of OSM mRNA and protein expression and phosphorylation of downstream P38 and ERK1 / 2.