癌变·畸变·突变 ›› 2009, Vol. 21 ›› Issue (3): 173-176.doi: 10.3969/j.issn.1004-616x.2009.03.004

• 论著 • 上一篇    下一篇

糖皮质激素联合IFN-γ对肺纤维化小鼠的治疗作用及机制探讨

鲁华山1, 张书玮1, 戴志强1, 刘 瑞2, 海春旭2   

  1. 1.第四军医大学口腔医学系,陕西 西安 710032; 2.第四军医大学军事毒理学
  • 收稿日期:2008-10-10 修回日期:2008-11-17 出版日期:2009-05-30 发布日期:2009-05-30

Effects and Mechanisms of Glucocorticoid Combined with IFN-γ on Pulmonary Fibrosis in Mice

LU Hua-shan1,ZHANG Shu-wei1,DAI Zhi-qiang1,LIU Rui2, HAI Chun-xu2   

  1. 1. College of Stomatology, Fourth Military Medical University, Xi'an 710032, Shaanxi;2. Department of Toxicology, Fourth Military Medical University, Xi'an 710032,Shaanxi, China
  • Received:2008-10-10 Revised:2008-11-17 Online:2009-05-30 Published:2009-05-30

摘要: 背景与目的: 观察糖皮质激素联合干扰素IFN-γ对肺纤维化小鼠的治疗作用。 材料与方法: 将雄性小鼠随机分为5组:阴性对照(生理盐水,NS)组、肺纤维化模型(博来霉素,BLM)组、地塞米松(DXM)治疗组、IFN-γ治疗组及DXM联合IFN-γ治疗组。后4组按3 mg/kg,气管内注入BLM建立肺纤维化模型,NS组采取相同手术方式,注入等量生理盐水。手术后1 d起,DXM组和联合组按 20 mg/kg皮下注射DXM,其余各组以相同方式给予生理盐水。从术后15 d起,IFN-γ组和联合组按0.01 μg/g皮下注射IFN-γ,其余各组以相同方式给予等量生理盐水。所有动物于术后22 d处死,显微镜下观察肺组织病理变化,取各组实验鼠肺组织匀浆液分别采用酸解法测定羟脯氨酸(Hyp)含量,免疫组化观察肿瘤坏死因子α (TNF-α) 的表达,荧光法测定还原型谷胱甘肽(GSH)与氧化型谷胱甘肽 (GSSG) 比值、丙二醛(MDA)含量以及总超氧化物歧化酶(T-SOD) 活性。 结果: DXM联合IFN-γ治疗组小鼠肺组织的病理评分与Hyp含量均低于BLM组及单独治疗组(P<0.05)。IFN-γ组小鼠肺组织的TNF-α表达最强,联合组的TNF-α表达介于DXM组和BLM组之间。联合组与BLM组及单独治疗组比较,GSH/GSSG升高,MDA含量减少,差异均有统计学意义(P<0.05)。各组之间,T-SOD活性的差异无统计学意义(P>0.05)。 结论: DXM与IFN-γ联合应用治疗小鼠肺纤维化效果明显优于单独用药。

关键词: 肺纤维化, 干扰素-γ, 糖皮质激素

Abstract: BACKGROUND AND AIM:To explore therapeutic effects of IFN-γ combined with glucocorticoid on pulmonary fibrosis in mice. MATERIALS AND METHODS: Mice were divided into five random groups: negative control(NS)group; model(bleomycine, BLM)group; dexamethasone (DXM) treatment group; IFN-γ treatment group; DXM combined IFN-γ treatment group. To establish the pulmonary fibrosis model, the last four groups received BLM intratracheally at a dose of 3 mg/kg, NS group received NS by the same way. From 1st day after BLM treatment, DXM group and combined group were treated with 20 mg/kg DXM subcutaneously. And from 15th day after BLM treatment, IFN-γ and combined groups were treated with IFN-γ 0.01 μg/g subcutaneously. After the different treatments, animals were killed at 22nd day. The pathological changes were examined, hydroxyproline content (Hyp)was assayed by acid hydrolyzation, TNF-α expression was shown by IHC, and GSH/GSSG ratio, MDA content as well as T-SOD activity were determined by fluorimetry. RESULTS: Pathological score and Hyp content of combined group were both significantly lower than BLM and individual treatment groups(P<0.05). TNF-α expression was highest in IFN-γ treatment group, while that of combined group was between the BLM and DXM treatment groups. Compared with BLM and individual treatment groups, GSH/GSSG ratio was higher but MDA content was lower in combined group(P<0.05). T-SOD activities were not significantly different among groups(P>0.05). CONCLUSION: The results indicated the effects of DXM combined with IFN-γ was better than their individual effect.

Key words: pulmonary fibrosis, IFN-γ, glucocorticoid