胸腺五肽对肺癌模型小鼠免疫功能及脾脏TLR4信号通路的作用

Effect of thymopentin on the immunologic function and TLR4 signal pathway in the spleen in mouse model of lung cancer

目的:研究胸腺五肽对肺癌模型小鼠免疫功能及脾脏Toll样受体-4(TLR-4)信号通路的作用。方法:40只C57BL/6小鼠随机分为正常对照组、模型对照组、环磷酰胺组和胸腺五肽组,除正常对照组外其他3组小鼠制作肺癌模型。造模成功后各组小鼠治疗2周,然后测定血液调节性T细胞(Treg细胞)和辅助性T细胞17(Th17细胞)水平及脾脏组织中TLR4、肿瘤坏死因子受体相关因子-6(TRAF-6)、核因子-κB(NF-κB)、激活蛋白-1(AP-1)mRNA和蛋白表达。结果:(1)胸腺五肽组小鼠血液Treg细胞和Th17细胞水平显著高于环磷酰胺组(P<0.01),而Treg细胞/Th17细胞值显著低于模型对照组(P<0.01);(2)胸腺五肽组小鼠脾脏TLR4、TRAF-6、NF-κB、AP-1mRNA和蛋白表达水平显著低于环磷酰胺组(P<0.01)。结论:肺癌小鼠接受环磷酰胺化疗时辅以胸腺五肽治疗可调节其免疫功能,下调脾脏TLR4信号通路TLR4、TRAF-6、NF-κB及AP-1的表达。

Objective: To study the effect of thymopentin on the immunologic function and Toll like recptor-4(TLR-4) signal pathway in the spleen in mouse model of lung cancer. Methods: Forty mice of C57BL/6 were randomly divided into normal control(NC) group,model control(MC) group,cyclophosphamide(CPM) group and thymopentin(THY) group. Except NC group,mice in other three groups were given subcutaneously Lewis lung cancer cells under right armpit to make mouse model of lung cancer. After two-week treatment,regulatory T cell(Treg cell) and T help cell 17(Th17 cells) were determined,and mRNA and protein of TLR4,tumor necrosis factor receptor-associated factor-6(TRAF-6),nuclear factor-κB (NF-κB) and activating protein-1(AP-1) were determined by transcription-polymerase chain reaction and Western-blotting. Results:(1)Compared with CPM group,the level of Treg and Th17 cells in THY group were increased significantly( P <0.01),and the ratio of Treg/Th17 was decreased significantly( P <0.01).(2)Compared with CPM group,the mRNA and protein level of TLR4,TRAF-6,NF-κB and AP-1 in the spleen of THY group were decreased significantly( P <0.01). Conclusion: Adjuvant therapy of thymopentin in the chemotherapy of cyclophosphamide for the mice with lung cancer can regulate the immunologic function and down-regulate the level of TLR4,TRAF-6,NF-κB and AP-1 in the TLR4 signal pathway in the spleen.