目的：测定转化生长因子-β₁(transforming growth factor-β₁， TGF-β₁)对甲状腺相关性眼病(thyroid-associated ophthalmopathy，TAO)患者纤维化眼外肌来源的成纤维细胞(orbital fibroblasts，OF)细胞Smad3，Smad4，Smad7基因表达的影响。

方法：采用实时荧光定量逆转录聚合酶连反应(real-time quantitative RT-PCR)观察5μg/L TGF-β₁刺激OF在不同时间点(0h； 15，30min； 1，2，4h)表达Smad3 mRNA，Smad4 mRNA，Smad7 mRNA的变化。

结果： 5μg/L TGF-β₁刺激OF 15min后，Smad3 mRNA的表达量已显著增加，为对照组的10.71倍，于1h达顶峰，为对照组的25.07倍(P<0.01)，持续近2h，然后呈下降趋势，4h基本恢复正常； 5μg/L TGF-β₁刺激OF 15min后，Smad4 mRNA的表达量开始增加，为对照组的1.54倍，于1h达顶峰，为对照组的15.99倍(P<0.01)，然后呈下降趋势，4h基本恢复正常； 5μg/L TGF-β₁刺激OF 30min后，Smad7 mRNA的表达量明显开始增加，为对照组的3.21倍，持续至4h为对照组的14.66倍(P<0.01)。

结论：TGF-β₁可活化眼眶成纤维细胞Smads信号通路。在一定的时间范围内，诱导OF表达Smad3 mRNA和Smad4 mRNA呈先增加后下降的趋势，而Smad7 mRNA表达则呈现持续增加的趋势，说明TGF-β₁/Smads这一纤维化相关的经典信号转导通路可能在TAO眼外肌纤维化机制中发挥了重要的作用。

AIM:To investigate the effects of transforming growth factor-β₁(TGF-β₁)on gene expression of main components of Smads family including Smad3, Smad4 and Smad7 in orbital fibroblasts(OF)of fibrosis extraocular muscle with thyroid -associated ophthalmopathy(TAO).

METHODS: OF were treated with 5μg/L TGF-β₁ at different time points(0min, 15min, 30min,1h, 2h and 4h), and real-time quantitative RT-PCR was performed to observe the effects of TGF-β₁ on the expression of Smad3, Smad4 and Smad7 mRNA.

RESULTS: The expression of Smad3 mRNA was 10.71 times to that of control group at 15min and 25.07 times at 1h(P<0.01); Smad4 mRNA was 1.54 times to that of control group at 15min and 15.99 times at 1h(P<0.01); Smad7 mRNA was 3.21 times to that of control group at 30min and 14.66 times at 4h(P<0.01).

CONCLUSION: TGF-β₁ up-regulate the expression of Smad3, Smad4, Smad7 mRNA in OF in a time dependent fashion, TGF-β₁/Smad pathway may play an important role in the pathogenesis of extraocular muscle fibrosis with TAO.

国家自然科学基金资助项目(No.81200719)