吉非替尼下调肿瘤抑制素M抑制博莱霉素诱导的小鼠肺纤维化  

Gefitinib downregulates the expression of OSM and inhibits bleomycin-induced pulmonary fibrosis

作　　者：郑林鑫 郑林鑫[2] 麦玉梅[2] 杜海坚[2] 李理[2] 李伟峰 

机构地区：[1]南方医科大学研究生学院,510515 [2]广州军区广州总医院呼吸内科,510010

出　　处：《免疫学杂志》2016年第4期305-309,共5页Immunological Journal

基　　金：广东省自然科学基金(2014A030313596;S2011010000511);广东省医学科学技术研究基金(A2015070);吴阶平医学基金会临床科研专项资助基金(320.6750.12330)

摘　　要：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。This study performed to study the change of oncostatin M（OSM） and its downstream signalingpathways in gefitinib-relieved pulmonary fibrosis in mice. KM female mice（n=36） were randomly divided into 3groups： the mice in control group were administered with saline aerosol intratracheally, the mice in fibrosis groupwere administered with bleomycin at a dose of 3 mg/kg aerosol intratracheally, while the mice in gefitinib group wereadministered with bleomycin at a dose of 3 mg/kg aerosol intratracheally and then were gastrically perfused withgefitinib at a dose of 20 mg/kg. All mice were sacrificed at 14 d after the treatment and the lungs were collected forhematoxylin eosin and Masson＇s trichrome staining to exam pathological change. The expression of OSM and α-SMAat m RNA and protein level were determined by RT-PCR and Western blotting; the protein levels of ERK1/2,P-ERK1/2, P38, and P-P38 were detected by Western blotting. Data showed that the pathological injury, collagenaccumulation, the m RNA expression of OSM and α-SMA, the protein levels of OSM, α-SMA, p-ERK1/2/ERK1/2,p-P38/P38 in the lung tissues in bleomycin group was significantly increased compared with that in control group,and the above-mentioned index in gefitinib group was significantly relieved compared with that in bleomycin group.Taken together, Gefitinib significantly relieves bleomycin-induced pulmonary fibrosis in mice. The underlyingmechanism may be involved in inhibiting the expression of OSM and downstream signaling pathways.

关 键 词：吉非替尼 肿瘤抑制素M(OSM) 博莱霉素 肺纤维化 

分 类 号：R563[医药卫生—呼吸系统]