柳氮磺胺吡啶和氢化泼尼松对大鼠结肠炎模型调节性T细胞的影响

目的 探讨CD4^＋ CD25^＋和CD8^＋ CD28^-调节性T细胞在2，4，6-三硝基苯磺酸（TNBS）诱发的大鼠实验性结肠炎模型的外周血、脾脏、结肠的改变及其作用。方法 建立TNBS实验性结肠炎大鼠模型。设对照组、建模后1周及3周组、柳氮磺胺吡啶（SASP）和氢化泼尼松（PSL）治疗组（在建模1周后分别每日给予SASP及PSL灌胃，治疗2周）共5组，用流式细胞仪检测各组外周血、脾脏和结肠黏膜上皮细胞内单个核细胞中CD4^＋ CD25^＋和CD8^＋ CD28^-调节性T细胞比例的变化；肠道积分评定组织学变化。结果 成功建立了TNBS大鼠模型。CD4^＋ CD25^＋ T细胞：建模后第1周在外周血、脾、结肠均较对照组升高，至第3周已恢复至对照组水平，SASP治疗后无变化，PSL治疗后在外周血、脾、结肠均明显低于建模后3周组。CD8^＋ CD28^- T细胞：建模第1周在外周血、脾、结肠均较对照组升高，至第3周仍高于对照组水平，SASP治疗后在脾、结肠中较建模后3周组下降。PSL治疗后在外周血、脾、结肠均明显低于建模后3周组。结论 CD4^＋ CD25^＋和CD8^＋ CD28^-这两种调节性T细胞可能在实验性结肠炎发病的不同阶段中起着一定作用，且以局部作用为主。CD8^＋ CD28^- T细胞可能与慢性炎症变化成正相关。PSL、SASP对大鼠实验性结肠炎均有明显疗效，PSL可减少CD8^＋ CD28^- T细胞量，较SASP疗效更显著。

Changes of T regulatory cells in rats with experimental colitis after drug treatment with SASP and PSL

Objective To explore the changes of CD4~+CD25~+ and CD8~+CD28~-T regulatory cells in rats with experimental colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) after drug treatment with salicylazosulfapyridine(SASP) and prednisolone(PSL).Methods The model of experimental colitis was established through TNBS enema.Thirty-nine adult SD rats were randomly divided into 5 groups: normal control group,experimental colitis model groups(1 week and 3 weeks),SASP therapeutic group,and PSL therapeutic group.The proportion of CD4~+CD25~+ and CD8~+CD28~-T regulatory cells in peri-(pheral) blood,spleen mononuclear cells,and intraepithelial lymphocytes of rat colons were determined by flow cytometry.Results The rat model of TNBS-induced colitis was established successfully.The CD4~+CD25~+ Tr in peripheral blood,spleen mononuclear cells,and intraepithelial lymphocytes of colon from experimental colitis model group(1 week) were higher than those from normal control group.The level of CD4~+CD25~+ Tr in experimental colitis model group was decreased to that of normal control group after 3 weeks,and did not change after SASP treatment.The level of CD4~+CD25~+ Tr of PSL-therapeutic group was significantly lower than that of experimental colitis model group.The CD8~+CD28~-Tr in peripheral blood,spleen mononuclear cells,and intraepithelial lymphocytes of colon were higher in experimental colitis model group than in normal control group from 1 week to 3 weeks.The CD8~+CD28~-Tr of SASP therapeutic group was lower than that of experimental colitis model group in spleen mononuclear cells and intraepithelial lymphocytes of colon.The CD8~+CD28~-Tr of PSL therapeutic group was significantly lower than that of experimental colitis model group in peripheral blood,spleen mononuclear cells,and intraepithelial lymphocytes of colon. Conclusion CD4~+CD25~+ and CD8~+CD28~T regulatory cells may be have relations with the different phases of colitis.CD8~+CD28~-T cells are positively correlated with chronic inflammation;SASP and PSL have decreased the proportion of CD8~+CD28~-T regulatory cells,and have therapeutic effects on experimental colitis,especially PSL.