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背景:溃疡性结肠炎(UC)是一种慢性非特异性结直肠炎症病变,在我国的发病率呈持续上升趋势,但其病因尚未完全阐明。目的:探讨UC患者结肠黏膜干扰素-γ(IFN-γ)、occludin、闭锁小带蛋白-1(ZO-1)的表达情况以及其间的相关性。方法:纳入2011年1月-2011年7月在天津医科大学总医院就诊的UC患者40例,选取20名同时期健康体检者作为正常对照组。采用免疫组化染色检测结肠黏膜IFN-γ、occludin、ZO-1蛋白的表达和分布,采用实时荧光定量PCR检测结肠黏膜occludin、ZO-1 mRNA表达。结果:IFN-γ主要表达于黏膜固有层中性粒细胞、单核细胞,而occludin、ZO-1主要表达于肠上皮细胞。UC组结肠黏膜IFN-γ蛋白表达较正常对照组显著升高(P=0.000),且活动期显著高于缓解期(P=0.004)。UC组结肠黏膜occludin、ZO-1蛋白和mRNA表达均较正常对照组显著降低(P<0.05),但不同疾病活动期组间差异无统计学意义(P>0.05)。IFN-γ蛋白表达与occludin、ZO-1蛋白表达均呈负相关(rs=-0.794和rs=-0.820,P均<0.05)。结论:IFN-γ可能通过下调紧密连接蛋白occludin、ZO-1表达,引起肠黏膜屏障功能损害,从而参与UC的发生。
BACKGROUND: Ulcerative colitis (UC) is a chronic nonspecific colorectal inflammation. The incidence in China is on the rise. However, its etiology has not yet been fully elucidated. Objective: To investigate the expression of interferon-γ (IFN-γ), occludin and ZO-1 in UC patients and the correlation between them. Methods: From January 2011 to July 2011, 40 patients with UC in Tianjin Medical University General Hospital were enrolled. Twenty healthy subjects of the same period were selected as the normal control group. The expression and distribution of IFN-γ, occludin, ZO-1 protein in colonic mucosa were detected by immunohistochemical staining. The occludin and ZO-1 mRNA expressions in colonic mucosa were detected by real-time fluorescence quantitative PCR. Results: IFN-γ was mainly expressed in neutrophils and monocytes in lamina propria, while occludin and ZO-1 were mainly expressed in intestinal epithelial cells. The expression of IFN-γ in colonic mucosa in UC group was significantly higher than that in normal control group (P = 0.000), and the active stage was significantly higher than that in remission stage (P = 0.004). The expression of occludin and ZO-1 protein and mRNA in colonic mucosa in UC group were significantly lower than those in normal control group (P <0.05), but there was no significant difference between the active disease groups in different groups (P> 0.05). The expression of IFN-γ was negatively correlated with the expression of occludin and ZO-1 protein (rs = -0.794 and rs = -0.820, all P <0.05). CONCLUSION: IFN-γ may be involved in the pathogenesis of UC by down-regulating the expression of tight junction protein occludin and ZO-1, causing intestinal mucosal barrier dysfunction.