Heuschen Gundi, Leowardi Christine, Hinz Ulf, Autschbach Frank, Stallmach Andreas, Herfarth Christian, Heuschen Udo A
Department of Surgery, St-Vincenz-Krankenhaus, Limburg, Germany.
Int J Colorectal Dis. 2007 Mar;22(3):293-301. doi: 10.1007/s00384-006-0133-6. Epub 2006 Jun 13.
The pathogenesis of pouchitis, major complication after restorative proctocolectomy, and ileal J pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC) is still unclear. Changes in intraluminal bacterial colonization and correlated changes of pouch mucosa are thought to play an important role. Toll-like receptors (TLRs) as part of the innate immune system are capable of recognizing bacterial antigens. Their activation can lead to secretion of proinflammatory mediators. In this study, TLR2, 3, 4, and 5 expression profiles in the pouch mucosa of patients with UC and IPAA were analyzed and correlated with pouchitis.
Clinical symptoms, endoscopy, and histology were assessed in 35 patients using the Heidelberg Pouchitis Activity Score to classify patients as either having pouchitis or not. TLR mRNA expression in normal ileal mucosa and pouch mucosa was investigated by performing semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR). The results of RT-PCR were associated with the pouchitis score.
In the analysis of all patients, TLR3 expression was decreased significantly whereas TLR5 expression was increased significantly in pouch mucosa compared to normal ileal mucosa (p-values 0.0076 and 0.016, respectively). A more detailed analysis upon dividing the patients into patients with and without pouchitis showed decreased TLR3 expression in the pouch mucosa only of patients without pouchitis (p-value=0.0067). TLR5 expression was increased in the pouch mucosa only of patients with pouchitis (p-value=0.023). No differences in TLR2 and 4 expression were found in either group.
Differential expression of TLR3 and 5 suggests bacterial involvement in the pathogenesis of pouchitis in patients with UC.
溃疡性结肠炎（UC）患者行结直肠切除回肠J袋肛管吻合术（IPAA）后，主要并发症袋炎的发病机制仍不清楚。腔内细菌定植的变化以及袋黏膜的相关改变被认为起着重要作用。作为固有免疫系统一部分的Toll样受体（TLR）能够识别细菌抗原。它们的激活可导致促炎介质的分泌。在本研究中，分析了UC和IPAA患者袋黏膜中TLR2、3、4和5的表达谱，并将其与袋炎相关联。
使用海德堡袋炎活动评分对35例患者的临床症状、内镜检查和组织学进行评估，以将患者分类为患有袋炎或未患有袋炎。通过进行半定量逆转录聚合酶链反应（RT-PCR）研究正常回肠黏膜和袋黏膜中TLR mRNA的表达。RT-PCR的结果与袋炎评分相关。
在所有患者的分析中，与正常回肠黏膜相比，袋黏膜中TLR3表达显著降低，而TLR5表达显著增加（p值分别为0.0076和0.016）。将患者分为有袋炎和无袋炎患者进行更详细的分析显示，仅在无袋炎患者的袋黏膜中TLR3表达降低（p值 = 0.0067）。仅在有袋炎患者的袋黏膜中TLR5表达增加（p值 = 0.023）。两组中TLR2和4的表达均未发现差异。
TLR3和5的差异表达表明细菌参与了UC患者袋炎的发病机制。
