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

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

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。

Objective To explore the changes of CD4 ^＋ CD25 ^＋ and CD8 ^＋ CD28 ^- T regulatory cells in rats with experimental colitis induced by 2, 4, 6- 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. 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 successfidly. The CD4 ^＋ CD25 ^＋ Tr in peripheral blood, spleen mononuclear cells, and intraepithehal 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 CD^8＋ 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. Conchusion 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.