益气活血中药对放射损伤大鼠肺组织TGF-β1和Ⅰ、Ⅲ型胶原合成的影响

Modulation by Yiqi Huoxue Recipe to the expression of TGF-β1 and the synthesis of procollagen typeⅠ,Ⅲ in radiation induced damage of lung of rats

目的:观察小剂量重复照射下不同时相大鼠肺组织转化生长因子-β1(TGF-β1)的表达和Ⅰ、Ⅲ型胶原纤维的动态变化,以及益气活血中药干预的影响,探讨益气活血中药防治放射性肺损伤的作用及机理。方法:96只Wistar种雌性大鼠随机分为照射加中药组(A组)30只、照射加氨溴索组(B组)30只、单纯照射组(C组)30只、正常对照组(D组)6只。用直线加速器对前3组大鼠右肺进行分次照射(5Gy/次,1次/w,累积剂量为30Gy),于照射开始后第4、6、8、12、26w5个时间点分别处死3组大鼠各6只,取肺组织切片行TGF-β1和Ⅰ、Ⅲ型胶原纤维免疫组化检测,观察各组大鼠肺组织不同时相TGF-β1的表达和胶原纤维含量的改变。结果:单纯照射组大鼠肺组织TGF-β1于照射第4w增高,第12w达到高峰;胶原纤维合成在第4w开始,第12w明显增快,至26w达到高峰。中药干预组各时相大鼠肺组织TGF-β1表达及Ⅰ、Ⅲ型胶原纤维增生程度均明显低于单纯照射组(P<0.05);各时相值与照射加氨溴索组近似,相比无统计学差异(P>0.05)。结论:在小剂量重复照射过程中,组织TGF-β1表达与组织胶原纤维合成有明显的同步性,而早期应用益气活血中药可抑制TGF-β1的表达,并减轻早期放射性肺炎的炎症反应和后期放射性肺纤维化的程度,因而对放射性肺损伤具有防治作用。

Objective： To observe the modulation by Yiqi Huoxue Recipe to the expression of transforming growth factor beta（TGF-β1） and the synthesis of collagen type Ⅰ,Ⅲ in radiation-induced lung injury of rats in different radiation time,and discuss the action mechanism of prevention and curative effect of Yiqi Huoxue Recipe.Methods： Total of 96 wistar rats were randomly allocated into irradiation group,irradiation with Yiqi Huoxue Recipe-treated group,irradiation with ambroxol-treated group and normal control group.The first three groups were irradiated at right hemithorax with a dose of 30Gy/6 fraction/5weeks.Animals were followed for 26 weeks after the first irradiation.We evaluated the deposition of collagens and the level of tissue TGF-β1 by immunoreactivity.Results： The pulmonary fibrosis was remarkable at the late phase in irradiation group.The fibrosis of treatment group were lighter than irradiation group.The collagen fibers increased from the fourth week after the first radiation and the proportion of type I and Ⅲ collagen of irradiation group was significantly higher than the treatment group（P0.05） and the control group（P 0.05）.Conclusion： Using Yiqi Huoxue Recipe earlier can reduce the synthesis of collagens effectively and inhibit radiation-reduced lung injury by restraining the expression of TGF-β1.