Faecalibacterium prausnitzii对实验性结肠炎大鼠Foxp3^+Treg细胞的影响

Effects of Faecalibacterium prausnitzii on Foxp3^+Treg Cells in Experimental Colitis Rats

背景:Fxop3+Treg细胞是一种免疫调节细胞,在免疫调节和维持机体免疫平衡中起重要作用。目的:研究Faecalibacterium prausnitzii(FP)对实验性结肠炎大鼠外周血和脾脏中CD4+CD25+Foxp3+Treg细胞的影响,从而初步探讨FP治疗溃疡性结肠炎(UC)的作用机制。方法:采用2,4,6-三硝基苯磺酸(TNBS)灌肠制备实验性结肠炎大鼠模型,将大鼠随机分为正常对照组、结肠炎组、FP组、FP上清液组、培养基组和双歧杆菌组。观察大鼠结肠大体形态损伤、组织学变化,以流式细胞术测定外周血和脾脏中CD4+CD25+Foxp3+Treg细胞比例,以ELISA法检测血浆IL-10、IL-12和TGF-β含量。结果:与正常对照组相比,结肠炎组结肠大体形态损伤明显,病理学评分显著增高(P<0.01);外周血和脾脏中CD4+CD25+Foxp3+Treg细胞比例显著降低(P<0.05);血浆IL-10和TGF-β含量显著降低(P<0.05),IL-12含量显著升高(P<0.01),IL-10/IL-12比值显著降低(P<0.01)。经FP、FP上清液和双歧杆菌治疗后,除血浆IL-10含量无明显差异外,其余指标均显著改善(P<0.05)。结论:FP及其上清液对TNBS诱导的实验性结肠炎大鼠有显著的治疗作用,其机制可能为提高外周血和脾脏中CD4+CD25+Foxp3+Treg细胞比例。

Foxp3CIreg cells is a kind of immunoregulatory cell that plays a critical role in immune regulation and maintaining immune balance. Aims： To investigate the effects of Faecalibacterium prausnitzii （FP） on CD4＋CD25＋Foxp3＋ Treg cells in peripheral blood and spleen in experimental colitis rats, so as to explore the mechanism of FP in the treatment of ulcerative colitis （UC）. Methods： The model of experimental colitis in rats was established by 2,4,6- trinitrobenzene sulfonic acid （TNBS） enema. The rats were randomly divided into six groups： normal control group, colitis group, FP group, FP supernatant group, bacteria culture medium group and bifidobacterium group. Macroscopic injury and histological change of colon were observed. The proportion of Foxp3Treg cells in peripheral blood and spleen were detected by flow cytometry, and levels of plasma IL-10, IL-12 and TGF-13 were determined by ELISA. Results： Compared with normal control group, macroscopic injury of colon was obvious in colitis group, histology score was significantly increased （P〈O.O1）, proportion of CD4＋CD25Foxp3Treg cells in peripheral blood and spleen was significantly decreased （P〈0.05）, levels of plasma IL-10 and TGF-13 were significantly decreased （P〈0.05） while level of plasma IL-12 was significantly increased （P〈O.01）, and the ratio of IL-10/IL-12 was significantly decreased （P〈0.O1）. After one week of treatment with FP, FP supernatant or bifidobacterium, all the above-mentioned indices were significantly improved （P〈 0.05） except level of plasma IL-10. Conclusions： The results indicate that FP and FP supernatant have an obvious therapeutic effect on TNBS-induced experimental colitis in rats, and the mechanism may be related to the increase of proportion of CD4＋CD25＋Foxp31＋reg cells in peripheral blood and spleen.