干扰素-γ对染矽尘小鼠肺脏肿瘤坏死因子-α和转化生长因子-β_1蛋白表达的影响

Effects of IFN-γ on TNF-α and expression of TGF-β_1 in experimental silicosis mice

目的探讨实验性矽肺纤维化小鼠模型支气管肺泡灌洗液(BALF)中肿瘤坏死因子(TNF)-α及肺组织转化生长因子(TGF)-β1的变化及干扰素-γ(IFN-γ)对其的调节作用。方法雌性ICR小鼠随机分为矽肺模型组、IFN-γ治疗组和对照组,每组32只。矽肺纤维化小鼠模型通过气管内暴露法(气管内注入SiO2粉尘混悬液)建立,对照组气管内注入0.1ml生理盐水。建模成功后,矽肺模型组及对照组每日腹腔内注射生理盐水0.3ml,IFN-γ治疗组每日腹腔内注射1.0×104/0.3mlIFN-γ,至处死为止。每组气管暴露后不同时间(7、14、21、28d)分别处死8只小鼠。用ELISA方法测定3组小鼠BALF中TNF-α水平,用免疫组织化学法测定矽肺组织中TGF-β1蛋白的表达,及IFN-γ治疗对二者的影响。结果矽肺模型小鼠肺组织TGF-β1表达在染尘后的7、14、21、28d时明显高于对照组(P均<0.01),表达高峰是染尘后的7d;IFN-γ治疗组IFN-γ治疗后的7、14、21、28d肺组织TGF-β1表达显著低于矽肺模型组(P<0.01或P<0.05),但仍高于对照组(P均<0.01)。矽肺模型组BALF中TNF-α水平明显高于对照组(P<0.01或P<0.05);IFN-γ治疗组IFN-γ治疗后TNF-α水平显著低于矽肺模型组(P均<0.05),但仍高于对照组。结论本文结果显示,IFN-γ对实验性小鼠肺纤维化具有一定的抑制作用,IFN-γ可能通过抑制TNF-α水平及TGF-β1在肺组织中的表达来抑制肺纤维化的发生发展。

Objective To research the variation of tumor necrosis factor-α（TNF-α） in broncho-alveolar lavage fluid（BALF） and expression of transforming growth factor-β1（TGF-β1）in lung tissue in experimental silicotic fibrosis model of mice,and effects of Interferon-γ（IFN-γ） on them.Methods Ninty-six femail ICR mice were randomly divided into three groups：silicotic fibrosis model group,IFN-γ treated group and control group（n=32,each）.Silicotic fibrosis model were constructed by intratracheal exposure method（intratracheal injecting SiO2 suspension）,mice of control group were administered by intraperitoneal infusion of 0.9% NaCl solution（0.1 ml）.After model build,mice were administered by intraperitoneal infusion of 0.9% NaCl solution（0.3 ml）every day in silicotic fibrosis model group and control group,but IFN-γ treated group were administered by intraperitoneal injecting IFN-γ（1.0 × 104 /0.3 ml,per day）.Eight mice in each group were respectively killed at day 7,14,21 and 28.The level of TNF-α in BALF was determined by ELISA,and the expression of TGF-β1 in lung tissue was analyzed by immunohistochemistry.The effects of IFN-γ on them were observed.Results At day 7,14,21 and 28,the expressions of TGF-β1 in lung tissue in different time point after inbreathing SiO2 suspension were all significantly increased in silicotic fibrosis model group comparing with the control group（all P 〈 0.01）.The rush hour of expression was at day 7.At day 7,14,21 and 28 after the treatment of IFN-γ,the expressions of TGF-β1 in lung tissue were notably decreased comparing with the silicotic fibrosis model group（P 〈 0.01 or P 〈 0.05）,but higher than those in the control group（all P 〈 0.01）.The level of TNF-α in BALF of silicotic fibrosis model group was significantly increased comparing with the control group（all P 〈0.05）.Level of TNF-α in BALF was decreased in IFN-γ treated group comparing with the silicotic fibrosis model group（P 〈 0.05）,but still higher than those in control group（all P 〈 0.05）.Conclusions IFN-γ may restrain the process of lung fibrosis and inhibit the improvement of lung fibrosis by means of preventing the expression of TGF-β1 and the level of TNF-α in mice of silicotic fibrosis.