益气活血中药对放射损伤大鼠肺组织转化生长因子和胶原纤维的影响

Modulation by Yiqi Huoxue Recipe on Tansforming Growth Factor and Collagens Synthesis in Lung of Rats with Radiation Induced Damage

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(transforming growth factor beta1,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。用直线加速器对前三组大鼠右肺进行分次照射(5Gy/次,1次/周,累积剂量为30Gy),于照射开始后第4、6、8、12、26周5个时间点分别处死三组大鼠各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,对照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病理改变。结果单纯照射组大鼠肺组织TGF-β1于照射第4周增高,第12周达到表达高峰;胶原纤维合成在第4周开始,第12周明显增快,至26周达到高峰。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 expressions of transforming growth factor beta 1 （TGF-β1）,changes of collagen types I and III in the lung of rats with radiation-induced injury,effects of Yiqi Huoxue Recipe on them,and explore discuss the prevention and treatment effects and the mechanism of Yiqi Huoxue Recipe on radiation-inguced lung injury.Methods Ninety-six female Wistar rats were randomly allocated into 4 groups：irradiation alone （IA,n=30）,Yiqi Huoxue Recipe treatment after irradiation （YT,n=30）,ambroxol treatment after irradiation （AT,n=30） and normal control （n=6）.The first three groups were irradiated at right hemithorax with a total dose of 30 Gy/6 Fraction/5 weeks.The animals were followed-up for 26 weeks after the first irradiation.The collagen deposition and the level of TGF-β1 were assayed by immunohistochemistry.Results There was obvious pulmonary fibrosis at the late phase in IT group.Fibrosis was lighter in treatment groups than in IT group.Collagen fibers increased fourth week after the first irradiation and collagen types I and Ⅲ levels were significantly higher in IA group than the treatment groups （P0.05） and normal control group （P0.05）.Conclusion Early administration of Yiqi Huoxue Recipe can effectively reduce the synthesis of collagens and alleviate radiation-reduced lung injury by inhibiting expression of TGF-β1.