雾化吸入γ-干扰素对放射性肺损伤重建的拮抗作用

目的 观察超声雾化吸入γ-干扰素(IFN-γ)对大鼠放射性肺损伤早期组织重建的拮抗作用,并初步探讨其作用机制。方法 将动物分为照射对照组和照射+IFN-γ拮抗组。于照前3d每日雾化吸入IFN-γ,分别于照后10、20和30d肺组织取材,制备石蜡切片,进行苏木素伊红(HE)、天狼猩红和α-平滑肌肌动蛋白(α-SMA)免疫组织化学染色;Western blot检测Ⅳ型胶原合成变化;ELISA检测MMP-2、-9和TIMP-1含量变化。结果 照射＋IFN-γ组与照射对照组比较,肺泡隔增宽程度明显减轻,Ⅰ、Ⅲ型胶原合成和α-SMA表达明显减少;照射后Ⅳ型胶原表达呈上升趋势,但IFN-γ吸入组较对照组为低;吸入IFN-γ10d可降低MMP-2和TIMP-1表达,而MMP-9表达升高;吸入30d 三者表达均下降。结论 IFN-γ对辐射引起的肺损伤具有明显的治疗作用,其可能的作用机制是IFN-γ降低TIMP-1表达,解除对MMP-9的抑制,进而降解Ⅳ型胶原,拮抗辐射引起的肺损伤后重建。

Antagonist effect of Interferon-γ aerosol inhalation on pulmonary remodeling after γ-ray irradiation

Objective To observe the antagonistic effect of interferon-γ aerosol inhalation on pulmonary remodeling after γ-ray irradiation, and explore its mechanisms. Methods The Wistar rats were randomly divided into irradiation control group and irradiation + lntederon-γ antagonist group, which proceeded IFN-γaerosol inhalation 3 days before 20 Gy 60 Co γ-ray irradiation, then were sacrificed at 10, 20, 30 days after irradiation. Conventional histopathologieal sections of lung tissue were prepared, which were stained immunohistochemicaUy for α-SMA and Sirius red. The contents of collagen Ⅳ were determined by Western blot.The expression of MMP-2, MMP-9 and TIMP-1 in lung homogenate was detected by ELISA. Results The widen degrees of interalveolar septum, the deposition of collagen Ⅰ,Ⅲ, and the expression of α-SMA decreased significantly in IFN-γ treatment group as compared with those in the irradiation control group. The expression of collagen Ⅵ appeared an elevation trend, but this phenomenon attenuated after IFN-γ was used. The levels of MMP-2 and TIMP-1 decreased 10 days after administration with IFN-γ, but the opposite trend appeared for MMP-9. The expression of MMP-2, MMP-9 and TIMP-1 decreased 30 days after administration with IFN-γ.Conclusion IFN-γ is effective in alleviating pulmonary injuries induced by irradiation in rats, possibly by decreasing the expression of TIMP-1 to relieve the inhibition to MMP-9, then degrading collagen Ⅳ to antagonize remodeling after lung injury.