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-  2018 

两种表皮生长因子抑制剂下调肿瘤抑制素 M 抑制博来霉素诱导的小鼠肺纤维化

DOI: doi:10.7507/1671-6205.201712029

Keywords: 肺纤维化, 表皮生长因子酪氨酸激酶抑制剂, 吉非替尼, 厄罗替尼, 肿瘤抑制素 M

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Abstract:

目的比较两种表皮生长因子酪氨酸激酶抑制剂(EGFR-TKI)吉非替尼和厄罗替尼对肿瘤抑制素 M(OSM)及下游通路的调节作用,以及对博来霉素诱导小鼠肺纤维化的干预作用。方法将 40 只 SPF 级雌性昆明小鼠随机分为对照组(生理盐水气管内雾化)、博来霉素组(博来霉素 3 mg/kg 气管内雾化)、吉非替尼组(博来霉素 3 mg/kg 气管内雾化后吉非替尼 20 mg·kg–1·d–1 灌胃)以及厄罗替尼组(博来霉素 3 mg/kg 气管内雾化后厄罗替尼 25 mg·kg–1·d–1 灌胃)。实验第 14 d 使用小动物 CT 对小鼠进行胸部 CT 检查,检查完毕后收集小鼠肺组织,行 HE、Masson 染色,Western blot 法检测肺组织 α 平滑肌肌动蛋白(α-SMA)、OSM、JAK1、p-JAK1、STAT3、p-STAT3 蛋白表达水平。结果吉非替尼和厄罗替尼处理后,小鼠胸部 CT 影像中肺部渗出及纤维化病灶较博来霉素组明显减少,肺组织病理损伤及纤维化损伤均较博来霉素组明显减轻(均 P<0.05),α-SMA 蛋白、OSM 蛋白、p-JAK1/JAK1、p-STAT3/STAT3 表达较博来霉素组明显下调(均P<0.05)。吉非替尼和厄罗替尼的上述作用无显著差异(均P>0.05)。结论两种表皮生长因子酪氨酸激酶抑制剂吉非替尼和厄罗替尼均能抑制博来霉素诱导的小鼠肺纤维化,其抑制作用相近,机制可能与下调 OSM 蛋白的表达以及下游 JAK/STAT 通路的磷酸化密切相关

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