健脾利湿汤治疗轻中度溃疡性结肠炎的疗效及其对调节T细胞功能影响的机制研究

Efficacy and mechanism of Jianpi Lishi decoction in the treatment of patients with mild to moderate ulcerative colitis by regulating the function of Treg cells

关键词:  溃疡性结肠炎  调节T细胞  穿孔素  颗粒酶B

Key words:  ulcerative colitis  regulatory T cells  perforin  granzyme B

摘要:

[目的] 观察健脾利湿汤治疗轻中度溃疡性结肠炎（UC）的临床疗效，并从调节T细胞（Treg）功能角度探讨其作用机制。[方法] 将59例UC患者随机分为2组，对照组口服美沙拉嗪肠溶片，健脾利湿组口服健脾利湿汤，持续治疗3个月。观察患者治疗前后主要症状评分、疗效指数、生活质量的改善情况；并采集正常人及患者外周血，ELISA法测定白介素-1β（IL-1β）和转化生长因子-β1（TGF-β1）含量。反转录实时定量聚合酶链式反应（RT-qPCR）法测定外周血Foxp3、穿孔素和颗粒酶B mRNA的水平。[结果] 经治疗，患者腹痛、腹泻、脓血便症状明显改善，且健脾利湿组改善效果明显优于对照组（P<0.05）。治疗3个月后，两组患者在胃肠症状、全身症状、情感能力和社会能力等方面的生活质量均较治疗前明显提高（P<0.05）；且健脾利湿组的生活质量明显优于对照组（P<0.05）。与正常人相比，治疗前两组患者外周血中IL-1β水平较高，而TGF-β水平较低；Foxp3 mRNA表达水平较低，而穿孔素和颗粒酶B mRNA表达水平较高，差异均具有统计学意义（P<0.01）；经过治疗，两组患者上述细胞因子及基因表达均向相反方向变化，与本组治疗前相比差异有统计学意义（P<0.05，P<0.01），且健脾利湿组的改善效果更为明显（P<0.05）。[结论] 健脾利湿汤通过调节Treg细胞的数量和功能，增强其免疫抑制功能，抑制穿孔素/颗粒酶B对靶细胞的杀伤作用，以此减轻肠道组织的炎症反应。

Abstract:

[Objective] In this study, the clinical efficacy of Jianpi Lishi decoction on mild to moderate ulcerative colitis (UC) and mechanisms associated with the function of Tregs were investigated.[Methods] Altogether 59 patients with mild to moderate UC were enrolled and randomly allocated to the control and Jianpi Lishi groups. The control group received salbutamol enteric-coated tablets, and the Jianpi Lishi group was given Jianpi Lishi decoction orally. The treatment process would be lasted for 3 months. The main symptom scores, curative effect index and the quality of life of patients were observed before and after treatment. The concentrations of IL-1β and TGF-β1 in peripheral blood were measured by enzyme-linked immunosorbent assay (ELISA) and the mRNA levels of Foxp3, perforin and granzyme B were determined by RT-qPCR.[Results] After treatment, the above symptoms were improved significantly, and the effect of "Jianpi Lishi" group was much better than that of the control group (P<0.05). After 3 months of treatment, the quality of life in gastrointestinal symptoms, systemic symptoms, affective ability and social ability of the two groups were significantly higher than those before treatment (P<0.05), and the quality of life was significantly better in the Jianpi Lishi group when compared with the control group (P<0.05). Compared with normal subjects, the levels of IL-1β in peripheral blood were higher in the two groups before treatment, while the level of TGF-β was lower; the mRNA level of Foxp3 was lower, and the mRNA levels of perforin and granzyme B were higher (P<0.05 or P<0.01). After treatment, the levels of above-mentioned cytokines and genes were changed to the opposite direction with significant differences (P<0.05 or P<0.01), and the improvement effect of Jianpi Lishi group was more obvious than the control group (P<0.05).[Conclusion] Jianpi Lishi decoction can enhance the immunosuppressive function by regulating the number and function of Tregs, and inhibit the killing effect of perforin/granzyme B on target cells, so as to reduce the inflammatory reaction of intestinal tract.