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。     

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-羟色胺转运体基因多态性与肠易激综合征的相关性

目的:探讨SERT基因启动子区5-HTTLPR和内含子2 VNTRs多态性在肠易激综合征(IBS) 中的意义．方法:采用PCR方法对51例腹泻型IBS(D- IBS)、58例便秘型IBS(C-IBS)、38例便秘腹泻交替型IBS(A-IBS)患者与48例健康对照者SERT基因启动子区5-HTTLPR和内含子2 VNTRs多态性进行比较分析．结果:C-IBS组L／L基因型及L等位基因频率显著高于对照组(31．0％vs 8．3％,X2=8．229, P<0．05;47．4％vs29．2％,X2=7．342,P<0．05), D-IBS组S／S基因型频率和S等位基因频率显著高于A-IBS和C-IBS组(S／S:56．9％vs 36．8％, 36．2％,P<0．05;S:71．6％vs 56．6％,52．6％, P<0．05),L／L基因频率显著低于A-IBS和C-IBS 组(9．8％vs 28．1％,P<0．05)．IBS各组与对照组之间内含子2 VNTRs多态性分布无显著性差异(P>0．05)．结论:具有L／L基因型和L等位基因的人更易患C-IBS,具有S／S基因型和S等位基因的人更易患D-IBS,L／L基因型可能是D-IBS的保护因素之一．     

5-羟色胺与肠易激综合征关系的研究进展

肠易激综合征(IBS)是一种由胃肠功能紊乱引起的疾病,国内外研究表明IBS与5-羟色胺(5-HT)关系密切,5-HT能使IBS患者的肠道运动增加、对液体的吸收减少和内脏敏感性增高,调控胃肠运动、分泌、吸收及感觉等复杂功能,故5-HT与IBS患者腹痛、腹泻和内脏感觉异常等症状密切相关。     

5羟色胺在肠易激综合征中的作用

肠易激综合征(IBS)是一个复杂的胃肠功能失调性疾病,包括胃肠动力、内分泌及内脏感觉等的异常.其临床特点为慢性的、或复发性的腹部疼痛或不适,包括排便习惯和大便性状异常,症状从轻到重.5羟色胺(5-HT)是一种广泛存在于中枢神经系统和胃肠道的神经递质,具有多种生物学功能.近年来其在调节胃肠道运动方面的作用逐渐受到重视,尤其在IBS发病机制及治疗中的作用受到越来越多的关注.     

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.     

肠易激综合征患者一氧化氮和5-羟色胺含量的改变

１材料和方法１．１材料按照１９８６年成都会议制定的肠易激综合征（ＩＢＳ）科研病例选择标准，从临床上以腹泻为主要症状的患者中筛选出ＩＢＳ患者１５例，其中男６例，女９例，平均年龄４５岁．正常对照组共１３例，来自本院工作人员，其中男６例，女７例，平均年龄３...     

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。     

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.     

5-羟色胺与冷刺激诱发肠易激综合征症状关系的研究

目的探讨女性腹泻型肠易激综合征（IBS）患者冷刺激前后5-羟色胺（5-HT）释放与症状发生间的关系，旨在阐明冷刺激诱发IBS症状过程中的5-HT机制。方法共纳入32例女性腹泻型IBS患者和21名女性健康对照者。应用高效液相色谱法测定受试者空腹时及饮用220ml 37℃温水、同体积4℃冷水后30、60、90、120、150、180min时血浆（去除血小板）中5-HT、5-羟吲哚乙酸（5-HIAA）浓度。同时问卷调查所有受试者腹痛／腹部不适、腹胀、腹泻等症状的发生情况，并对其严重程度进行评分。结果空腹状态下，腹泻型IBS患者和健康对照者血浆5-HT和5-HIAA浓度差异无统计学意义（P〉0．05）。饮冰水后30min[（48．65±11．03）比（35．52±6．29）nmol／L]、60min[（62．79±11．58）比（40．99±6．18）nmol／L]、90min[（69．56±9．26）比（45．48±6．33）nmol／L]、120min[（58．64±25．00）比（38．73±6．40）nmol／L]、150min[（46．59±7．96）比（34．43±5．79）nmol／L]时腹泻型IBS患者血浆5-HT浓度显著升高（P值均〈0．05），5-HIAA浓度与5-HT呈伴行改变，5-HT代谢率（5-HIAA：5-HT）无明显变化，5-HT及5-HIAA峰值浓度及曲线下面积明显升高（P〈0．01）。饮温水时则无以上差异。饮冷水后19例腹泻型IBS患者出现腹痛或腹部不适、腹胀、排便急迫感和（或）腹泻等症状，其血浆5-HT浓度较未发生以上症状的患者明显升高，且其5-HT浓度与症状严重程度呈正相关（r=0．714，P=0．001）。结论女性腹泻型IBS患者进冷食后症状加剧可能与血浆5-HT水平升高有关。     

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.     

Recent advances in pharmacological treatment of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a highly prevalent functional disorder that reduces patients’ quality of life. It is a chronic disorder characterized by abdominal pain or discomfort associated with disordered defecation in the absence of identifiable structural or biochemical abnormalities. IBS imposes a significant economic burden to the healthcare system. Alteration in neurohumoral mechanisms and psychological factors, bacterial overgrowth, genetic factors, gut motility, visceral hypersensitivity, and immune system factors are currently believed to influence the pathogenesis of IBS. It is possible that there is an interaction of one or more of these etiologic factors leading to heterogeneous symptoms of IBS. IBS treatment is predicated upon the patient’s most bothersome symptoms. Despite the wide range of medications and the high prevalence of the disease, to date no completely effective remedy is available. This article reviews the literature from January 2008 to July 2013 on the subject of IBS peripherally acting pharmacological treatment. Drugs are categorized according to their administration for IBS-C, IBS-D or abdominal pain predominant IBS.     

Genetic epidemiology of irritable bowel syndrome

Irritable bowel syndrome(IBS) is the most common functional gastrointestinal disorder characterized by presence of abdominal pain or discomfort associated with altered bowel habits. It has three main subtypes- constipation predominant IBS(C-IBS),diarrhea predominant IBS(D-IBS) and IBS with mixed featuresof both diarrhea as well as constipation(M-IBS). Its pathophysiology and underlying mechanisms remain elusive. It is traditionally believed that IBS is a result of multiple factors including hypersensitivity of the bowel,altered bowel motility,inflammation and stress. Initial studies have shown familial aggregation of IBS suggesting shared genetic or environmental factors. Twin studies of IBS from different parts of world have shown higher concordance rates among monozygotic twins than dizygotic twins,and thus suggesting a genetic component to this disorder. Multiple studies have tried to link single-nucleotide polymorphisms(SNPs) to IBS but there is little evidence that these SNPs are functional. Various molecules have been studied and investigated by the researchers. Serotonin,a known neurotransmitter and a local hormone in the enteric nervous system,has been most extensively explored. At this time,the underlying gene pathways,genes and functional variants linked with IBS remain unknown and the promise of genetically-determined risk prediction and personalize medicine remain unfulfilled. However,molecular biological technologies continue to evolve rapidly and genetic investigations offer much promise in the intervention,treatment and prevention of IBS.     

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.     

褪黑激素与肠易激综合征

肠易激综合征是一种原因不明的慢性肠功能紊乱性疾病，其发病机制尚不清楚。其治疗方法也在不断改进中，褪黑激素对肠易激综合征的治疗有着积极的作用。