Chen Ying, Chen Jie, Dong Jing, Liu Wanyang
Division of Pneumoconiosis, School of Public Health, China Medical University, 92 North 2nd, Shenyang 110001, PR China.
Toxicol Lett. 2005 Mar 15;155(3):353-60. doi: 10.1016/j.toxlet.2004.10.011.
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.
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。