不同分期溃疡性结肠炎结肠黏膜血清素再摄取转运体的表达分析
Expression of serotonin reuptake transporter in ulcerative colonic mucosa at different stages

摘要：目的 检测血清素再摄取转运体(SERT)在不同分期溃疡性结肠炎(UC)结肠黏膜中的表达情况，探讨炎症性肠病患者肠易激综合征(IBS)样症状的发病机制。方法 纳入2011年至2015年31名UC患者，其中男性17名，女性14名，平均年龄(47.2±5.3)岁；活动期患者11名，缓解期患者20名。收集病史资料及常规结肠镜检查检测患者UC分期，NBI成像进行黏膜分型(常规/非常规血管型)，HE染色评估黏膜Matts组织学分级，免疫组织化学方法和RT-PCR检测SERT、色氨酸羟化酶-1(TPH-1)及炎性因子的表达，高通量PCR分析系统检测炎症及成血管相关基因表达谱。分析SERT表达与IBS症状、炎症因子及成血管相关基因表达的相关性。8周龄C57B/6J雄性小鼠共40只，分为模型组和对照组，利用右旋葡聚糖苷钠(DSS)构建结肠炎模型，动态检测不同时间点SERT和炎症基因在小鼠结肠黏膜的表达。结果 缓解期患者黏膜SERT基因相对浓度和组织学表达强度显著高于活动期黏膜(P<0.001)。SERT基因表达水平与IBS样症状呈负相关性(P<0.001)。活动期黏膜IL-8 mRNA相对表达水平显著高于缓解期黏膜(P<0.001)。Matts组织分级结果、IL-8 mRNA相对浓度与SERT mRNA的相对浓度呈负相关(r=－0.38，P<0.001；r=－0.59，P=0.002) 。TPH-1 mRNA的表达与黏膜IL-8 mRNA表达无显著相关性(r=0.28，P=0.100)。常规血管型黏膜SERT mRNA表达高于非常规血管型，组织学分级及TPH-1 mRNA表达低于非常规血管型。IL-1、IL-8、CXCL3、CXCL5、CXCL1在非血管型黏膜组织中显著增高。小鼠结肠炎模型组SERT表达显著低于对照组(P=0.001)。结论 SERT在UC患者活动期黏膜中表达下调，在非常规血管型缓解期黏膜中表达下调；SERT下调参与溃疡性患者IBS样症状形成的病理过程，该过程与炎症以及成血管机制相关。
ABSTRACT: Objective To detect the expression of serotonin reuptake transporter (SERT) in mucosa of patients with ulcerative colitis (UC) of different stages and investigate the pathogenesis of irritable bowel syndrome (IBS) in UC patients. Methods We enrolled 31 UC patients (17 males and 14 females) from 2011 to 2015. Their average age was (47.2±5.3) years old. There were 11 patients at active stage and 20 patients at remission stage. We collected the history data and used the results of conventional colonoscopy which determined the stages of UC. Colonic mucosa in remission could be divided into regular and irregular vascular patterns by narrow band imaging. Matts？？ degree was evaluated by HE staining. The expressions of SERT, TPH-1 and inflammatory factor were detected by Real-time PCR and IHH. Expressions of inflammation- and angiogenesis-related genes in colonic mucosa with unregular pattern and regular vessel pattern were detected by using high-throughput PCR analysis system. The expressions of SERT and inflammatory genes in colonic mucosa were detected dynamically at different time points in mouse model of colitis by DSS. All data were treated with SPSS 21.0. Results The relative concentration of SERT gene and tissue expression in intestinal epithelial cells (active mucosa) were significantly lower than that of inactive mucosa (P<0.001). The expression of SERT was negatively correlated with the IBS-like symptoms. The relative concentration of IL-8 mRNA in intestinal epithelial cells (active mucosa) was significantly higher than that of inactive mucosa (P<0.001). The relative concentration of SERT mRNA was negatively related to the relative concentration of IL-8 mRNA and the