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干扰素γ在大鼠矽肺模型中的抗纤维化作用

Antifibrotic effect of interferon gamma in silicosis model of rat.

作者信息

Chen Ying, Chen Jie, Dong Jing, Liu Wanyang

机构信息

Division of Pneumoconiosis, School of Public Health, China Medical University, 92 North 2nd, Shenyang 110001, PR China.

出版信息

Toxicol Lett. 2005 Mar 15;155(3):353-60. doi: 10.1016/j.toxlet.2004.10.011.

Abstract

This study presents the antifibrotic effect of interferon gamma (IFN-gamma) in silicosis of rats. Wistar rats were received saline or 20 mg of quartz by intratracheal instillation. The next day after instillation, silicosis model of rats were daily treated IFN-gamma (1.0 x 10(5) units/rat) or saline by intramuscular route. At 1 month or 2 months after instillation, rats were sacrificed to determine hydroxyproline content and observe the change of fibrosis and expression of interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) in the lung of rats. The hydroxyproline content of IFN-gamma treated groups was significantly lower than that of quartz groups (P<0.05). At 1 month after instillation, there were Stage II and II+ of silicotic nodules in quartz group; however, in IFN-gamma treated group only cellular nodules (Stage I) were observed. At 2 months after instillation, there was Stage II+ and III of silicotic nodules in quartz group. In IFN-gamma treated group Stage II was found. The expressions of IL-4 (2.19+/-0.90, 0.61+/-0.22, respectively) and TGF-beta1 (1.37+/-0.31, 1.76+/-0.72, respectively) in IFN-gamma treated groups were significantly lower than those in quartz groups (IL-4: 3.33+/-1.27, 1.99+/-0.80; TGF-beta1: 3.67+/-0.63, 4.90+/-1.11, respectively; P<0.05 or P<0.01). It may be concluded that the decreased expression of IL-4 and TGF-beta1 may be associated with decreased hydroxyproline synthesis, which then results in decreased lung fibrosis.

摘要

本研究呈现了干扰素γ(IFN-γ)对大鼠矽肺的抗纤维化作用。将Wistar大鼠经气管内滴注给予生理盐水或20mg石英。滴注后第二天,矽肺模型大鼠每日经肌肉途径给予IFN-γ(1.0×10⁵单位/只大鼠)或生理盐水。在滴注后1个月或2个月,处死大鼠以测定羟脯氨酸含量,并观察大鼠肺中纤维化的变化以及白细胞介素-4(IL-4)和转化生长因子-β1(TGF-β1)的表达。IFN-γ治疗组的羟脯氨酸含量显著低于石英组(P<0.05)。滴注后1个月,石英组出现II期和II+期矽结节;然而,IFN-γ治疗组仅观察到细胞结节(I期)。滴注后2个月,石英组出现II+期和III期矽结节。IFN-γ治疗组发现II期。IFN-γ治疗组中IL-4(分别为2.19±0.90、0.61±0.22)和TGF-β1(分别为1.37±0.31、1.76±0.72)的表达显著低于石英组(IL-4:分别为3.33±1.27、1.99±0.80;TGF-β1:分别为3.67±0.63、4.90±1.11;P<0.05或P<0.01)。可以得出结论,IL-4和TGF-β1表达的降低可能与羟脯氨酸合成减少有关,进而导致肺纤维化减轻。

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