溃疡性结肠炎黏膜中β防御素2与肿瘤坏死因子α和白细胞介素1β的表达及相互关系

Expression and significance of mucosal β-defensin-2, TNFα and IL-1β in ulcerative colitis

目的研究β防御素2（HBD2）与促炎因子TNFα和IL-1β在溃疡性结肠炎（UC）肠黏膜中的表达及相互关系，旨在探讨其在UC发病中的作用。方法选择2004年12月-2005年12月四川大学华西医院消化科确诊的UC患者，计算疾病活动度（UCAI），对UC进行病理学分级。免疫组化、实时荧光定量PCR研究结肠黏膜组织中HBD2和TNFα、IL-1β的表达及其相互关系。结果35例UC患者中轻度10例，中度13例，重度12例。病理分级Ⅰ级11例，Ⅱ级13例，Ⅲ级11例。UCAI评分与病理学分级之间呈正相关（P〈0．05）。UC患者结肠黏膜HBD2表达显著高于正常对照组（P〈0．05），且在黏膜的炎症部位显著高于非炎症部位，且与TNFα和IL-1β的表达呈正相关。结论HBD2的表达与促炎因子TNFα和IL-1β的表达密切相关，两者相加可能是结肠炎炎症反应放大、损伤加重、持续迁延的原因之一。

Objective To investigate the expression and significance of human β-defensin-2 （HBIY2）, TNFet and IL-1β in ulcerative colitis （UC）. Methods Thirty-five patients with active UC diagnosed by the department of gastroenterology in West China Hospital were included in this study. Ulcerative colitis disease activity index （UCAI） was assessed and the pathological grades of UC were classified, lmmunohistochemistry assay and real-time quantitative PCR were used for the expression of HBD2, TNFα, IL-1β in colonic mucosa of UC. Results Among the 35 patients with UC, 10 cases were mild, 13 moderate and 12 severe. Of the 35 cases, there were 11 with grade Ⅰ , 13 grade Ⅱ and 11 grade Ⅲ lesion according to Truelove criteria. The score of UCAI had positive correlation with pathological grading （r =0.890, P 〈 0.01 ）. The expressions of HBD2, TNFet, IL-1β in colonic mucosa of UC with immunohistochemistry and real-time quantitative PCR were significantly higher than those in healthy control （P 〈 0.05 ） ; the expressions increased gradually with the severity of pathological grade and there was a higher expression of them in inflamed area than in non-inflamed（ P 〈 0. 05）. A good positive correlation was also found between HBD2 and other inflammatory cytokines. Conclusions It is shown that there is a higher expression of HBD2 in colonic mucosa as compared with healthy control, a higher expression of it in inflamed area than in non-inflamed area and a positive correlation of expression between HBD2 and pro-inflammatory cytokines such as TNFα and IL-1β, implying that HBD2 and pro-inflammatory cytokines are interdependent and interactive playing an important role in magnifying and aggravating inflammatory injury in UC.