低剂量X线辐射损伤后IFN-γ分泌性T、NK细胞修复能力及熟地的保护作用

Recovery of IFN-γ-secreting T and NK cells after low dose X-ray radiation injury and the protective effect of Prepared Radix Rehmanniae

目的探讨低剂量辐照后IFN-γ分泌性T、NK细胞修复能力及熟地的保护作用。方法采用X线2.5Gy建立小鼠辐照模型,部分辐照小鼠建立黑色素瘤肺癌模型或进行熟地治疗。采用流式细胞术检测各组小鼠Tc1、Th1和NK1细胞及其IL^(-1)2R、IL^(-1)5R表达。RT-qPCR检测IL^(-1)2、IL^(-1)5、STAT4和T-bet转录水平。结果辐照后4 d内,Th1、Tc1和NK1细胞显著降低(P<0.05,P<0.01);IL^(-1)2R、IL^(-1)5R在Th1、Tc1细胞表达下降,在NK1细胞表达升高(P<0.05)。辐照d 8,NK1和Tc1细胞恢复至正常或超正常水平,但Th1仍低于正常水平(P<0.05);辐照小鼠较对照肿瘤小鼠肿瘤载量明显升高(P<0.01)。与辐射组对比,熟地可提高NK1、Tc1、Th1比例和数量(P<0.05,P<0.01),减少辐照后肿瘤载量(P<0.05)。结论辐照后Th1细胞修复能力较弱,影响整体抗肿瘤能力;熟地可促进辐射后IFN-γ分泌性T和NK细胞修复,减少肿瘤转移风险。

Aim To investigate the recovery of IFN-γ-secreting T and NK cells after low dose X-ray irradiation and the protective effect of Prepared Radix Rehmanniae(PRR).Methods X-ray 2.5Gy was used to establish a mouse irradiated model,and some irradiated mice were used to establish a melanoma lung cancer metastasis model or to be treated by PRR.The proportion and number of Tc1,Th1 and NK1 cells with the phenotypes of IL^(-1)2R and IL^(-1)5R were detected by flow cytometry.The transcription levels of IL^(-1)2,IL^(-1)5,STAT4 and T-bet were detected by RT-qPCR.Results Within four days after irradiation,Th1,Tc1 and NK1 cells were significantly reduced(P<0.05,P<0.01).The expression of IL^(-1)2R and IL^(-1)5R decreased in Th1 and Tc1 cells,and increased in NK1 cells(P<0.05).On day 8 of irradiation,NK1 and Tc1 cells recovered or exceeded basic level,but Th1 was still lower than normal level(P<0.05),and tumor load of irradiated mice increased significantly(P<0.01).Compared with radiation group,the proportion and absolute numbers of NK1,Tc1 and Th1 were up-regulated by PRR(P<0.05,P<0.01),and tumor load was down-regulated(P<0.05).Conclusions The impaired reconstitution of Th1 cells after irradiation affects the anti-tumor ability.PRR promotes the recovery of IFN-γ-secreting T and NK cells after radiation and reduces the risk of tumor metastasis in mice.