李会荣 崔昭 梁博

[摘要] 目的 探討溃疡性结肠炎（UC）患者肠道菌群含量变化及其与炎性因子及TOLL样受体（TLRs）分子的相关性。 方法 选取2016年2月～2018年8月河北省保定市第二医院收治的UC患者82例作为观察组，另选取同期行健康体检的志愿者70例作为对照组，检测白细胞介素（IL）-4（IL-4）、IL-6、肿瘤坏死因子-α（TNF-α）、肠道菌群含量情况以及TLRs分子（TLR4、TLR9）表达情况并进行比较，采用Pearson相关性分析TLRs分子表达与肠道菌群、炎性因子的相关性。 结果 观察组肠杆菌、拟杆菌、肠球菌以及梭杆菌含量高于对照组，而乳杆菌、双歧杆菌含量则低于对照组，差异均有统计学意义（均P < 0.05）。观察组TLR4、TLR9、IL-6、TNF-α高于对照组，IL-4低于对照组，差异均有统计学意义（均P < 0.05）。Pearson相关性分析结果显示，UC患者TLR4、TLR9与肠杆菌、拟杆菌、肠球菌、梭杆菌、IL-6、TNF-α呈正相关（r > 0，P < 0.05），与乳杆菌、双歧杆菌、IL-4呈负相关（r < 0，P < 0.05）。结论 UC患者体内肠道菌群失调，其可通过促进TLRs分子表达进而提高促炎因子水平，降低抑炎因子水平，介导肠黏膜炎性反应。

[关键词] 溃疡性结肠炎;肠道菌群;炎性因子;TOLL样受体;相关性

[中图分类号] R574.62          [文献标识码] A          [文章编号] 1673-7210（2020）07（a）-0156-04

[Abstract] Objective To investigate the changes of intestinal flora in patients with ulcerative colitis （UC） and its correlation with inflammatory factors and TOLL-like receptors （TLRs） molecules. Methods A total of 82 patients with UC admitted to the NO.2 Hospital of Baoding Hebei Province from February 2016 to August 2018 were selected as the observation group， and 70 volunteers who underwent physical examination during the same period were selected as the control group. The levels of interleukin （IL）-4， IL-6， tumor necrosis factor-α （TNF-α）， intestinal flora content and the expression of TLRs molecules （TLR4 and TLR9） were detected and compared. Pearson correlation was used to analyze the correlation between TLRs expression and intestinal flora and inflammatory factors. Results The contents of Enterobacter， Bacteroides， Enterococcus and Fusobacterium in the observation group were higher than those in the control group， while the contents of Lactobacillus and Bifidobacterium in the observation group were lower than those in the control group， with statistically significant differences （all P < 0.05）. TLR4， TLR9， IL-6 and TNF-α in the observation group were higher than those in the control group， and IL-4 was lower than that in the control group， with statistically significant differences （all P < 0.05）. Pearson correlation analysis showed that TLR4 and TLR9 in UC patients were positively correlated with Enterobacter， Bacteroides， Enterococcus， Fusobacterium， IL-6 and TNF-α （r > 0，P < 0.05）， but negatively correlated with Lactobacillus， Bifidobacterium and IL-4 （r < 0，P < 0.05）. Conclusion In patients with UC， intestinal flora is dysregulated， which can promote the expression of TLRs molecules to increase the level of pro-inflammatory factors， reduce the level of anti-inflammatory factors， and mediate the inflammatory response of intestinal mucosa.

TOLL基因最早于果蝇体内发现，其编码的跨膜受体蛋白称TLR，TLR是一个新型的细胞受体蛋白家族，而TLRs则是体内重要的模式识别受体，具有识别多种病原菌的能力，通过下游髓样分化因子88以促进核因子-κB进入细胞核，最终启动多种炎性因子表达[14-15]。其中TLR4能识别脂多糖，同时能介导肠上皮细胞对细菌胞壁成分的反应，有研究表明，高TLR4水平可通过影响肠上皮细胞对细菌胞壁成分的信号传递，促进炎性因子的增殖，导致肠道炎性反应[16];TLR9能够识别细菌的非甲基化的胞嘧啶-磷酸-鸟嘌呤基序，可介导胞嘧啶-磷酸-鸟嘌呤基序激活T细胞、DC细胞、B细胞等多种免疫细胞，诱导免疫应答，参与UC的发生发展[17]。本研究中观察组TLR4、TLR9高于对照组，可见肠黏膜中的TLR4、TLR9参与UC的病情进展，与陈胜等[18]学者研究结果一致。……