溃疡性结肠炎患者肠道菌群变化与细胞因子、TLRs分子表达的相关性研究

目的探讨溃疡性结肠炎患者肠道菌群变化与细胞因子、TOLL样受体(Toll-like receptors,TLRs)分子表达的相关性。方法将2015年6月—2016年12月在山东省医学科学院第三附属医院确诊并接受治疗的溃疡性结肠炎患者78例作为试验组,同时选择未患溃疡性结肠炎的80例健康者作为对照组。分别对试验组和对照组进行肠道菌群检测,肠黏膜TLR2、TLR4、TLR5、TLR9分子表达检测和外周血IL-4、IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达检测,分析炎性细胞因子和TLRs表达与肠道菌群变化的关系。结果试验组双歧杆菌、乳杆菌含量明显低于对照组(P均0.05),拟杆菌、肠杆菌、肠球菌、梭杆菌含量明显高于对照组(P均0.05);试验组肠黏膜组织中TLR2、TLR4、TLR5、TLR9表达明显高于对照组(P均0.05);试验组外周血IL-4表达低于对照组,IL-6、IL-17、IL-23、TNF-α等炎性细胞因子表达高于对照组(P均0.05)。Pearson相关性分析显示,TLR2、TLR4、TLR5、TLR9表达与拟杆菌、肠杆菌、肠球菌含量呈正相关,与双歧杆菌、乳杆菌含量呈负相关;与IL-6、IL-17、IL-23、TNF-α表达呈正相关,与IL-4表达呈负相关。结论溃疡性结肠炎患者正常肠道菌群平衡被打破,促炎因子表达增加,抑炎因子表达减少,TLRs分子表达增加。肠道菌群紊乱可能通过增强TLRs分子表达来促进促炎因子的分泌,介导肠黏膜炎性反应。

Correlation of intestinal microflora with cytokines and Toll-like receptors expression in patients with ulcerative colitis

Objective To investigate the correlation of the changes of intestinal flora with the expression of cytokines and Toll-like receptors (TLRs) molecules in patients with ulcerative colitis.MethodsFrom June 2015 to December 2016, 78 patients with ulcerative colitis diagnosed and treated in the Third Affiliated Hospital of Shandong Academy of Medical Sciences were selected as the experimental group, and 80 healthy subjects were chosen as the control group. The intestinal flora detection, expression of TLR2, TLR4, TLR5, TLR9 molecules in intestinal mucosa, expression of IL-4, IL-6, IL-17, IL-23, TNF-α and other inflammatory cytokines in peripheral blood in the experimental group and control group were analyzed respectively. The correlation of inflammatory cytokines and the expression of TLRs with the change of intestinal flora was also analyzed.ResultsThe contents of bifidobacterium and lactobacillus in the experimental group were significantly lower than those in the control group (P<0.05), while the contents of bacteroides, enterobacter, enterococcus and fusobacterium were significantly higher (P<0.05). The expressions of TLR2, TLR4, TLR5 and TLR9 in intestinal mucosa of the experimental group were significantly higher than those of the control group (P<0.05). The expression of IL-4 in peripheral blood of the experimental group was lower than that of the control group, and the expressions of IL-6, IL-17, IL-23, TNF-α and other inflammatory cytokines were higher than that of the control group (P<0.05). Pearson correlation analysis showed that TLR2, TLR4, TLR5, TLR9 expressions were positively correlated with the contents of bacteroides, enterobacter and enterococcus, and negatively correlated with bifidobacterium and lactobacillus; it was also positively correlated with IL-6, IL-17, IL-23, TNF-α expression and negatively correlated with IL-4 expression.ConclusionsNormal intestinal flora balance of ulcerative colitis patients is broken, the expression of proinflammatory cytokines increases, the expression of proinflammatory factors decreases, and the expression of TLRs molecules increases. The disorder of intestinal flora promotes the secretion of proinflammatory cytokines by enhancing the expression of TLRs molecules and mediates the inflammatory response of the intestinal mucosa.