溃疡性结肠炎患者肠道菌群紊乱与Th17/Treg及其分泌炎性细胞因子免疫平衡的关系-现代医学

溃疡性结肠炎患者肠道菌群紊乱与Th17/Treg及其分泌炎性细胞因子免疫平衡的关系

作者：刘姝王飞

单位：四川省攀枝花市中西医结合医院, 四川攀枝花 617000

分类号：R574.1

出版年·卷·期（页码）：2020·39·第七期（862-867）

摘要：

目的：探讨溃疡性结肠炎（UC）患者肠道菌群紊乱与Th17/Treg免疫平衡及其分泌炎性细胞因子的关系。方法：收集2016年3月至2018年6月在我院消化科收治的UC患者作为研究对象，根据病情进展分为缓解期UC组和活动期UC组，以同期体检的健康者作为对照组。实时定量聚合酶链反应（qRT-PCR）法分析各组肠道内肠杆菌、肠球菌、拟杆菌、双歧杆菌和乳酸杆菌的数目，HE染色、免疫组织化学观察并计算病变部位的病理变化和炎性因子表达水平，流式细胞术检测血浆Th17、Treg细胞百分比，Pearson相关分析法分析肠道菌群与炎性因子及Th17、Treg细胞的相关性。结果：与对照组相比，活动期UC组和缓解期UC组肠道中拟杆菌、双歧杆菌、乳酸杆菌数目明显减少，肠杆菌、肠球菌数目增多；活动期UC和缓解期UC病变部位IL-2、IL-6、IL-17表达升高，IL-10表达下降；血浆中Treg细胞比例降低，Th17细胞比例和Th17/Treg值升高，活动期UC组变化更明显，差异有统计学意义（P<0.05）。Pearson相关分析显示，IL-2、IL-6、IL-7表达水平及Th17细胞比例与双歧杆菌、乳酸杆菌、拟杆菌呈负相关，与肠球菌、肠杆菌呈正相关；IL-10表达水平、Treg细胞比例与双歧杆菌、乳酸杆菌、拟杆菌呈正相关，与肠球菌、肠杆菌呈负相关。结论：肠道菌群紊乱与UC的发生及病情进展密切相关，肠道菌群紊乱可能通过诱导Th17/Treg免疫失衡调节相应炎性介质的分泌影响UC的发生。

Objective:To investigate the relationship between intestinal flora disorder and Th17/Treg immune balance and secretion of inflammatory cytokines in patients with ulcerative colitis(UC). Methods: The UC patients admitted to our hospital from March 2016 to June 2018 were enrolled as the study subjects. According to the progression of the disease, they were divided into the UC group in the remission period and the UC group in the active period. The healthy subjects in the same period were used as the control group. Real-time quantitative polymerase chain reaction(qRT-PCR) analysis of the number of Enterobacter, Enterococcus, Bacteroides, Bifidobacteria and Lactobacillus in each group. HE staining, immunohistochemistry was used to observe pathological changes and calculate expression levels of inflammatory factors in lesions. Flow cytometry was used to detect the percentages of plasma Treg and Th17 cells. The correlation analysis method was used to analyze the correlation between intestinal flora and inflammatory factors and Treg and Th17 cells.Results: Compared with the control group, the number of Bacteroides, Bifidobacteria and Lactobacillus in the intestinal UC group and the UC group in the active phase decreased, and the number of Enterobacter and Enterococcus increased. The expression of IL-2, IL-6 and IL-17 in the active stage UC and remission stage UC lesion sites was increased, and the expression of IL-10 wasdecreased. The proportion of Treg cells in plasma was decreased, the ratio of Th17 cells and Th17/Treg ratio wereincreased, and the changes in active UC group were more significant. The differences were statistically significant(P<0.05).Pearson's correlation analysis showed that the expression levels of IL-2, IL-6, IL-7 and Th17 cells werenegatively correlated with Bifidobacterium, Lactobacillus and Bacteroides, and positively correlated with Enterococcus and Enterobacter(P<0.05),IL-10 expression level and Treg cell ratio were positively correlated with Bifidobacterium, Lactobacillus and Bacteroides, and negatively correlated with Enterococcus and Enterobacter (P<0.05).Conclusion:Intestinal flora disorder is closely related to the occurrence of UC and the progression of the disease. Intestinal flora disorder may affect the secretion of UC by regulating the secretion of Th17/Treg immune imbalance.

参考文献：

[1] 李丹丹,袁星星,杨磊,等.解毒化瘀汤对活动期溃疡性结肠炎Th17/Treg细胞及其细胞因子的影响[J].中国中医急症,2018,27(1):16-19.
[2] BELTRÁN B,SÁEZ-GONZÁLEZ E,MORET I,et al.Adsorptive granulocyte/monocyte apheresis use in severe ulcerative colitis and determination of changes in plasma cytokines[J].J Clin Apheresis,2018,33(1):99-103.
[3] GUBATAN J,MITSUHASHI S,LONGHI M S,et al.Higher serum vitamin D levels are associated with protective serum cytokine profiles in patients with ulcerative colitis[J].Cytokine,2018,103:38-45.
[4] 马旭园,代志峰,王慧超,等.溃疡性结肠炎患者肠道菌群的变化及其与IL-23/IL-17轴的关系[J].中国病理生理杂志,2018,34(5):124-132.
[5] 中华医学会消化病学分会炎症性肠病协作组。中国炎症性肠病诊断治疗规范的共识意见[J].胃肠病学,2007,47(1):139-145.
[6] 范红芬,卢茸.营养支持及干预对重度溃疡性结肠炎患者肠道菌群、Th细胞免疫应答、炎症反应的影响[J].海南医学院学报,2017,23(23):3223-3226.
[7] CHEN L,WILSON J E,KOENIGSKNECHTM J,et al.Corrigendum:NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth[J].Nat Immunol,2017,18(5):541.
[8] 彭林艳,冯利波.溃疡性结肠炎患者血清 IDO 含量检测及其与机体 Treg/Th17,Th1/Th2 免疫平衡的相关关系[J].海南医学院学报,2018,24(22):1967-1970.
[9] KESHTELI A H,MILLAN B,MADSENK L.Pretreatment with antibiotics may enhance the efficacy of fecal microbiota transplantation in ulcerative colitis:a meta-analysis[J].Mucosal Immunol,2017,10(2):565.
[10] 庞艳华,吴东方,马亚会,等.白细胞介素-6在溃疡性结肠炎模型小鼠Th17/Treg细胞失衡中的作用[J].胃肠病学和肝病学杂志,2018,27(5):15-18.
[11] WECHSLER J B,SZABO A,HSUC L,et al.Histamine drives severity of innate inflammation via histamine 4 receptor in murine experimental colitis[J].Mucosal Immunol,2018,11(3):861-870.
[12] ROSEN M J,KARNS R,VALLANCEJ E,et al.Mucosal expression of type 2 and type 17 immune response genes distinguishes ulcerative colitis from colon-only crohn's disease in treatment-naive pediatric patients[J].Gastroenterology,2017,152(6):1345.
[13] SANDBORN W J,SU C,SANDS B E,et al.Tofacitinib as induction and maintenance therapy for ulcerative colitis[J].N Engl J Med,2017,376(18):1723.
[14] 徐航宇,王彦礼,王敦方,等.高通量测序技术研究黄芩汤对溃疡性结肠炎大鼠肠道菌群的影响[J].药学学报,2017(11):1673-1682.
[15] PARAMSOTHY S,KAMM M A,KAAKOUSH N O.Multidonor intensive faecal microbiota transplantation for active ulcerative colitis a randomised placebo-controlled trial[J].Lancet,2017,389(10075):1218.
[16] TAN C X W,BRAND H S,BOER N K H D,et al.Gastrointestinal diseases and their orodental manifestations:Ulcerative colitis[J].B Dent J,2017,222(1):53-57.

服务与反馈：

【文章下载】【发表评论】【查看评论】【加入收藏】

提示：您还未登录，请登录！点此登录