无机砷暴露抑制小鼠肾脏CD4^+T淋巴细胞的免疫调节效应

Inorganic arsenic exposure suppresses immunomodulatory effect of renal CD4^+T lymphocytes in mice

目的探讨无机砷暴露对小鼠肾脏CD4^+T淋巴细胞分化能力的影响及其可能机制。方法雌性C57BL/6小鼠随机分为对照组、(2.5、5、10)mg/kg NaAsO2暴露组,每组10只。一次性灌胃方式染毒,染毒时间为24 h,对照组给予生理盐水。实时荧光定量PCR检测肾脏1型辅助T(Th1)细胞转录因子T细胞表达的T盒(T-bet)及细胞因子γ干扰素(IFN-γ),Th2细胞转录因子GATA结合蛋白3(GATA3)及细胞因子白细胞介素4(IL-4),Th17细胞转录因子维甲酸相关孤核受体γt(ROR-γt)及细胞因子IL-22,调节性T细胞(Treg)转录因子叉头盒转录因子3(FOXP3)及细胞因子转化生长因子β(TGF-β)的mRNA水平。采用商品化的试剂盒检测血清中过氧化氢酶(CAT)、总抗氧化能力(T-AOC),肾脏中丙二醛(MDA)、超氧化物歧化酶(SOD)水平。结果与对照组相比,砷暴露组小鼠体质量、肾脏质量及脏器系数无明显变化;砷暴露组小鼠Th1细胞、Th2细胞、Th17细胞和Treg转录因子T-bet、GATA3、ROR-γt、FOXP3及相关细胞因子IFN-γ、IL-4、IL-22、TGF-β的mRNA水平明显降低;砷暴露小鼠血清中CAT活性及T-AOC水平明显降低。此外,砷明显增加肾脏MDA水平,减少SOD活性。结论无机砷暴露抑制肾脏T细胞亚群功能,诱导肾脏氧化损伤。

Objective To investigate the effects of inorganic arsenic exposure on the differentiation of renal CD4^+T lymphocytes and the possible mechanism.Methods Female C57BL/6 mice were randomly divided into control group,(2.5,5,10)mg/kg NaAsO2 exposure groups,10 mice in each group.As was administered once intragastrically for 24 hours,and control mice were treated with normal saline.Real-time fluorescence quantitative PCR was used to detect T helper type 1(Th1)cell-specific transcription factor T-box expressed in T cells(T-bet)and IFN-γ,Th2 cell-specific transcription factor GATA-binding protein 3(GATA3)and interleukin 4(IL-4),Th17 cell-specific transcription factor retinoic acid related orphan nuclear receptorγt(ROR-γt)and cytokine IL-22,regulatory T cells(Tregs)-specific transcription factor forkhead box P3(FOXP3)and cytokine transforming growth factor-β(TGF-β)mRNA levels.We used commercial kits to detect catalase(CAT)activity and total antioxidant capacity(T-AOC)in serum as well as renal malondialdehyde(MDA)and superoxide dismutase(SOD).Results Compared with the control group,the body mass,renal mass and kidney index of the mice in all arsenic-treated groups have no significant changes.The levels of the master transcription factors T-bet,GATA3,ROR-γt and FOXP3 as well as related cytokines IFN-γ,IL-4,IL-22 and TGF-βof Th1,Th2,Th17 cells and Tregs decreased in the arsenic-treated groups.Serum CAT activity and T-AOC level in the arsenic-treated mice dropped greatly.In addition,arsenic markedly increased renal MDA level while decreased SOD activity.Conclusion Inorganic arsenic exposure can suppress renal T cell subpopulation function and induce renal oxidative injure.