5-羟色胺转运体基因多态性与肠易激综合征

肠易激综合征(IBS)是临床最常见的功能性肠病,其病因及发病机制还不完全清楚。5-羟色胺(5-HT)是参与调节胃肠道运动和分泌功能的重要神经递质,在IBS的发病中有重要意义。5-羟色胺转运体(SERT或5-HTT)蛋白再摄取神经突触间隙的5-HT,对其起灭活作用。大量研究表明,SERT基因多态性与IBS各型间可能存在联系。     

5-羟色胺转运体与肠易激综合征

肠易激综合征(IBS)是临床最常见的功能性肠病,病因尚不清楚。5-羟色胺(5-HT)是脑-肠轴中的关键递质,它在胃肠运动和感觉,以及中枢情感调节中有重要意义。5-羟色胺转运体(SERT)是一种对5-HT有高度亲和力的跨膜转运蛋白,可将效应部位的5-HT迅速再摄取。大量的证据表明,SERT在IBS的发生和发展中发挥重要的作用。     

肠易激综合征患者5-羟色胺转运体的基因多态性

目的 探讨5-羟色胺转运体(SERT)基因多态性在肠易激综合征(IBS)中的意义。方法 用PCR方法对48例健康对照和30例便秘型IBS(C-IBS)、32例腹泻型IBS(D-IBS)和19例交替型IBS(A-IBS)患者SERT基因的VNTRs和5-HTTLPR区多态性进行研究。结果 VNTRs区：IBS患者STin2．12／10基因型频率明显高于对照组,各亚型间基因型频率差异无显著性。5-HTTLPR区：C-IBS组L／L频率显著高于D-IBS、A-IBS和对照组;D-IBS、A-IBS组IMS频率显著高于C-IBS组。C-IBS组12／12-L／L基因型联合的频率显著高于A-IBS和D-IBS组。结论 SERT基因VNTRs区STin2．12／10基因型可能与IBS相关,具有L／L基因型以及12／12-L／L基因型联合的人群可能更易患C-IBS,IMS基因型的人群易患D-IBS和A-IBS。     

5-羟色胺信号系统与肠易激综合征

5-羟色胺(5-HT)是参与调节胃肠道运动和分泌功能的重要神经递质,5-HT信号系统异常可导致胃肠动力及分泌功能异常、内脏高敏感性,与IBS的病理生理改变相关。此文旨在探讨5-HT信号系统在IBS肠道运动和感觉的调节、脑肠轴异常、精神症状、神经保护等方面的作用。     

肝郁脾虚型肠易激综合征与5-羟色胺转运体基因多态性的关系

[目的]探讨肝郁脾虚型肠易激综合征（IBS）与5-羟色胺转运体（SERT）基因多态性的关系。[方法]用多聚酶链式反应技术（PCR）对50例肝郁脾虚型IBS患者与96例健康对照者SERT基因的启动子区（5-HTTLPER）和内含子2可变数目串联重复序列（VNTRs）多态性进行研究。[结果]肝郁脾虚型组5-HTTLPR基因频率分布是S／S 40．0％，L／S54．0％，L／L11．1％。健康对照组的分布频率是S／S57．3％，L／S35．4％，L／L7．3％。2组之间比较差异无统计学意义（P〉0．05），但肝郁脾虚型组的L／S基因频率比对照组明显升高（P〈0．05）。2组VNTRs区的多态性比较差异无统计学意义（P〉0．05）。[结论]拥有L／S基因型可能是肝郁脾虚型IBS的多个易患因素之一。     

5-羟色胺转运体基因多态性与功能性肠病研究进展

功能性肠病（functional bowel disorders，FBD）是指症状主要起源于中下胃肠道的功能性胃肠病，依据临床症状分为肠易激综合征（irritable bowel syndrome，IBS）、功能性腹胀（functional bloating）、功能性便秘（functional constipation）、功能性腹泻（functional diarrhea）和非特异性肠功能紊乱（unspecified functional bowel disorders）。FBD是消化系统常见疾病，由于其病因及发病机制尚不明确，临床缺乏疗效理想而又安全可靠的治疗方法。     

5-羟色胺转运体在肠易激综合征腹痛机制中的研究

目的 探究5-羟色胺转运体(SERT)在肠易激综合征腹痛机制中的作用.方法 构建新生大鼠肠易激综合征腹痛模型,在其成年后取其结肠、脑干、额前皮质组织,应用免疫组化及实时PCR法检测各组织SERT定位和表达,并对各组织中5-羟色胺进行半定量分析.结果 模型组与对照组大鼠结肠、脑干、额前皮质中SERT mRNA表达水平分别为13.95±2.05比8.65±1.33、52.69±22.59比13.82±5.71、0.48±0.17比0.17±0.14,结肠、脑干中SERT蛋白表达水平分别为13.19±3.82比21.35±4.49、2.47±0.44比4.55±0.92,差异均有统计学意义(P值均＜0.05),额前皮质SERT蛋白表达水平差异无统计学意义(4.68±0.48比4.46±0.69,P＞0.05).模型组大鼠结肠5-羟色胺较对照组表达水平增高(5.56±0.48比2.68士0.22),在中缝背核和额前皮质中则表达水平降低(分别为3.75±0.43比7.46±0.72、5.07±0.80比7.97±1.10,P值均＜0.05).结论 SERT在肠易激综合征大鼠结肠、脑干、额前皮质组织中表达降低,在脑、肠层面参与腹痛的发生发展.     

5-羟色胺转运体在肠易激综合征腹痛机制中的研究

Objective To investigate the role of serotonin transporter (SERT) in pathogenesis of abdominal pain in irritable bowel syndrome (IBS). Methods Neonatal SD rats were divided into control group and IBS abdominal pain model group which was established by colorectal distension.The colon, nucleus raphes dorsalis (NRD) and prefrontal cortex (FC) tissues were harvested when all rats grew into adults. Expressions of SERT and 5-HT were determined by real-time PCR and immunohistochemistry. Results The expression of SERT mRNA in colon, NRD and FC tissues in model and control group were 13.95±2.05 vs 8.65±1.33, 52.69±22.59 vs 13.82±5.71 and0.48±0.17 vs 0.17±0.14, respectively, with significant differences (all P values ＜0.05). The protein expression of SERT in colon and NRD,but not FC tissues,decreased in model group compared with control group (13.19±3.82 vs 21.35±4.49,2.47±0.44 vs 4.55±0.92, respectively, P＜0.05).Meanwhile, in comparison with control group, the expression of 5-HT in colon was significantly increased in model group (5.56±0.48 vs 2.68±0.22), but decreased in NRD and FC tissues (3.75±0.43 vs 7.46±0.72, 5.07 ± 0.80 vs 7.97 ±1.10, respectively, P＜0.05). Conclusions Low expression of SERT in brain and colon may attribute to the pathogenesis of abdominal pain in IBS.     

5-羟色胺转运体在肠易激综合征腹痛机制中的研究

Objective To investigate the role of serotonin transporter (SERT) in pathogenesis of abdominal pain in irritable bowel syndrome (IBS). Methods Neonatal SD rats were divided into control group and IBS abdominal pain model group which was established by colorectal distension.The colon, nucleus raphes dorsalis (NRD) and prefrontal cortex (FC) tissues were harvested when all rats grew into adults. Expressions of SERT and 5-HT were determined by real-time PCR and immunohistochemistry. Results The expression of SERT mRNA in colon, NRD and FC tissues in model and control group were 13.95±2.05 vs 8.65±1.33, 52.69±22.59 vs 13.82±5.71 and0.48±0.17 vs 0.17±0.14, respectively, with significant differences (all P values ＜0.05). The protein expression of SERT in colon and NRD,but not FC tissues,decreased in model group compared with control group (13.19±3.82 vs 21.35±4.49,2.47±0.44 vs 4.55±0.92, respectively, P＜0.05).Meanwhile, in comparison with control group, the expression of 5-HT in colon was significantly increased in model group (5.56±0.48 vs 2.68±0.22), but decreased in NRD and FC tissues (3.75±0.43 vs 7.46±0.72, 5.07 ± 0.80 vs 7.97 ±1.10, respectively, P＜0.05). Conclusions Low expression of SERT in brain and colon may attribute to the pathogenesis of abdominal pain in IBS.     

肠康方对肠易激综合征内脏高敏感模型大鼠脑肠轴中5-羟色胺转运体的作用

目的:探讨肠康方对肠易激综合征(irritable bowel syndrome,IBS)内脏高敏感模型大鼠脑-肠轴中5-羟色胺转运体(serotonin transporter,SERT)的作用.方法:将72只SD幼♂大鼠随机分为空白对照组和造模组.采用AL-Chaer方法造模,将成功造模后的大鼠随机分为模型组、阳性药物对照组、肠康方高剂量组、中剂量组及低剂量组.第70天取脑、肠组织制作标本,应用免疫组织化学技术检测SERT的表达.结果:IBS内脏高敏感模型大鼠具有肠黏膜与脑组织SERT的低表达(0.16±0.05,P<0.05;0.10±0.04,P<0.001);肠康方高剂量治疗后肠黏膜(0.41±0.11,P<0.001)与脑组织(0.19±0.05,P<0.001)中SERT表达水平显著增高;肠康方中剂量治疗后肠黏膜(0.36±0.10,P<0.001)与脑组织(0.14±0.03,P<0.05)SERT表达水平也显著增高.结论:肠康方可调控IBS内脏高敏感模型大鼠脑-肠轴中SERT表达来治疗IBS.     

Regulation of the serotonin transporter in the pathogenesis of irritable bowel syndrome

Serotonin(5-HT) and the serotonin transporter(SERT) have earned a tremendous amount of attention regarding the pathogenesis of irritable bowel syndrome(IBS). Considering that enteric 5-HT is responsible for the secretion, motility and perception of the bowel, the involvement of altered enteric 5-HT metabolism in the pathogenesis of IBS has been elucidated. Higher 5-HT availability is commonly associated with depressed SERT mR NA in patients with IBS compared with healthy controls. The expression difference of SERT between IBS patients and healthy controls might suggest that SERT plays an essential role in IBS pathogenesis, and SERT was expected to be a novel therapeutic target for IBS. Progress in this area has begun to illuminate the complex regulatory mechanisms of SERT in the etiology of IBS. In this article, current insights regarding the regulation of SERT in IBS are provided, including aspects of SERT gene polymorphisms, microR NAs, immunity and inflammation, gut microbiota, growth factors, among others. Potential SERT-directed therapies for IBS are also described. The potential regulators of SERT are of clinical importance and are important for better understanding IBS pathophysiology and therapeutic strategies.     

Effect of Lactobacillus rhamnosus GG supernatant on serotonin transporter expression in rats with post-infectious irritable bowel syndrome

AIM To evaluate the effect of Lactobacillus rhamnosus GG supernatant(LGG-s) on the expression of serotonin transporter(SERT) in rats with post-infectious irritable bowel syndrome(PI-IBS).METHODS Campylobacter jejuni 81-176(1010 CFU/m L) was used to induce intestinal infection to develop a PI-IBS model. After evaluation of the post-infectious phase by biochemical tests, Dn A agarose gel electrophoresis, abdominal withdrawal reflex(AWR) test, and the intestinal motility test, four PI-IBS groups received different concentrations of LGG-s for 4 wk. The treatments were maintained for 1.0, 2.0, 3.0 or 4.0 wk during the experiment, and the colons and brains were removed for later use each week. SERT m Rn A and protein levels were detected by real-time PCR and Western blot, respectively.RESULTS The levels of SERT m Rn A and protein in intestinal tissue were higher in rats treated with LGG-s than in control rats and PI-IBS rats gavaged with PBS during the whole study. Undiluted LGG-s up-regulated SERT m Rn A level by 2.67 times compared with the control group by week 2, and SERT m Rn A expression kept increasing later. Double-diluted LGG-s was similar to undiluted-LGG-s, resulting in high levels of SERT m Rn A. Triple-diluted LGG-s up-regulated SERT m Rn A expression level by 6.9-times compared with the control group, but SERT m Rn A expression decreased rapidly at the end of the second week. At the first week, SERT protein levels were basically comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triplediluted LGG-s, which were higher than those in the control group and PBS-treated PI-IBS group. SERT protein levels in the intestine were also comparable in rats treated with undiluted LGG-s, double-diluted LGG-s, and triple-diluted LGG-s by the second and third weeks. SERT m Rn A and protein levels in the brain had no statistical difference in the groups during the experiment.CONCLUSION LGG-s can up-regulate SERT m Rn A and protein levels in intestinal tissue but has no influence in brain tissue in rats with PI-IBS.     

Genetic polymorphism in pathogenesis of irritable bowel syndrome

Irritable bowel syndrome(IBS)is a complex symptombased disorder without established biomarkers or putative pathophysiology.IBS is a common functional gastrointestinal disorder which is defined as recurrent abdominal pain or discomfort that has at least two of the following symptoms for 3 d per month in the past 3mo according to ROMEⅢ:relief by defecation,onset associated with a change in stool frequency or onset with change in appearance or form of stool.Recent discoveries revealed genetic polymorphisms in specific cytokines and neuropeptides may possibly influence the frequencies and severity of symptoms,as well as the therapeutic responses in treating IBS patients.This review gives new insights on how genetic determinations influence in clinical manifestations,treatment responses and potential biomarkers of IBS.