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

[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。

[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（P0.05）, and the quality of life was significantly better in the Jianpi Lishi group when compared with the control group（P0.05）. 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（P0.05 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.