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。     

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。     

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.     

肺动脉高压的5-羟色胺/5-羟色胺转运体机制研究进展

肺动脉高压是临床常见的以肺血管阻力进行性增加并伴有不可逆的血管构型重塑为特征的疾病.5-羟色胺作为一种血管活性物质,可以通过5-羟色胺转运体介导,诱导肺动脉平滑肌细胞增殖,促进肺中小动脉构型重塑.因此,揭示5-羟色胺及5-羟色胺转运体在肺动脉高压形成发展中的重要作用,探讨其成为抗肺动脉高压药物治疗新靶点的可能性具有重要意义.     

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。     

内脏高敏感大鼠肠道5-羟色胺转运体的变化以及中药肠吉安治疗的研究

目前认为肠易激综合征（IBS）的主要病理机制之一是内脏高敏感，5-羟色胺（5-HT）在内脏高敏感的发生中起重要作用，而5-HT主要通过5-HT转运体（SERT）调节。目的：研究内脏高敏感大鼠结肠黏膜5-HT和SERT的表达，并评估中药肠吉安对内脏高敏感的疗效。方法：18只Sprague-Dawley新生大鼠随机分为对照组、模型组、肠吉安治疗组，后两组制备内脏高敏感模型。对照组和模型组予0．9％NaCl溶液，肠吉安治疗组予0．9％NaCl溶液和中药肠吉安。比较各组腹壁回撤反射（AWR）评分，并取结肠组织行5．HT、SERT免疫组化染色。结果：与对照组相比，在10、20和40mmHg（1mm Hg=0．133kPa）压力结直肠扩张时，模型组大鼠AWR评分显著升高（P〈0.05），结肠黏膜5-HT表达显著增高（P〈0．05），SERT表达则降低（P〈0．05）。肠吉安治疗后，在较低压力下，AWR评分较模型组显著降低（P〈0．05），5-HT表达显著降低（P〈0．05），SERT表达则显著升高（P〈0．05）。结论：肠道SERT表达降低导致5-HT表达增高，可能是IBS大鼠内脏高敏感的重要机制之一，中药肠吉安可使两者在肠道的表达趋向正常，从而改善大鼠内脏高敏感。     

肠易激综合征重叠症的研究进展

肠易激综合征(IBS)是一种常见的以反复发作的腹痛或腹部不适伴排便频率或粪便性状改变为特征的功能性肠病,可单独发生,亦可与其他疾病并存。IBS除可与胃肠道疾病如胃食管反流病(GERD)、功能性消化不良(FD)、炎症性肠病(IBD)、显微镜肠炎(MC)、乳糜泻等重叠外,还可与非胃肠道疾病如焦虑症、哮喘等重叠。本文从流行病学和病理生理学角度对IBS重叠症作一综述。     

脑源性神经营养因子在肠道高敏感中的研究进展

内脏敏感性增高是肠易激综合征(IBS)重要的病理生理学机制之一。近年研究显示,脑源性神经营养因子(BDNF)过表达与IBS内脏高敏感密切相关。BDNF作为神经营养因子参与了神经元的存活、生长、发育、分化、再生过程。肠道组织中大量表达BDNF及其受体,对肠神经系统(ENS)的形成和功能具有调节作用,提示BDNF可能在肠道高敏感的发生机制中发挥重要作用。本文就BDNF在肠道高敏感中的研究进展作一综述。     

5-羟色胺信号系统在炎症性肠病发病机制中的地位

炎症性肠病(IBD)患者较易出现功能性肠道症状,这些症状往往与肠道活动性炎症关系不大,却与肠功能紊乱有关,说明IBD的发病在某些方面与肠易激综合征(IBS)相似。5-羟色胺(5-HT)信号系统异常可致胃肠动力、分泌功能异常和内脏高敏感性,与多种功能性胃肠病密切相关。而IBD的发病机制中亦存在功能性因素,提示IBD与IBS可能存在某些分子水平的联系,有必要对5-HT信号系统在IBD发病机制中的作用进行研究。     

小肠细菌过度生长在肠易激综合征中的研究进展

肠易激综合征(IBS)是一种常见的功能性胃肠病,其发病机制复杂。目前认为IBS与胃肠动力障碍、内脏高敏感、肠道感染、脑-肠轴功能紊乱、免疫活化等因素有关。最新研究表明小肠细菌过度生长(SIBO)在IBS的发病中亦起重要作用。本文就SIBO在IBS中的研究进展,包括病理生理机制、诊断、治疗等作一综述。     

肠易激综合征内脏高敏感的研究进展

肠易激综合征(IBS)是以腹痛或腹部不适并伴有排便习惯改变但无器质性病变的功能性胃肠疾病,其发病与多种因素有关。近年来,内脏高敏感(包括内脏痛觉过敏和痛觉异常)作为IBS的生物学标记受到广泛关注。本文就IBS内脏高敏感的的研究进展作一综述。     

Association Analysis of a Regulatory Variation of the Serotonin Transporter Gene with Severe Alcohol Dependence

The present study tested the hypothesis that the short, low activity variant of a biallelic polymorphism in the 5'regulatory region of the human serotonin transporter (5-HTT) gene confers susceptibility to severe alcohol dependence marked by severe withdrawal symptoms. Applying a phenotype-genotype strategy, our population-based association analysis included 216 German controls and an extreme sample of 103 severely affected alcoholics who were selected from 315 German alcohol-dependent subjects by a history of alcohol withdrawal seizure or delirium. The frequency of the short allele (S) was significantly increased in the severely affected alcoholics, compared with that in the controls ( X ²= 3.87, df = 1, nominal p = 0.049). The post-hoc exploration indicated that this allelic association resulted exclusively from a significant excess of the S/S genotype in the severely affected alcoholics ( p = 0.035), suggesting a recessively acting effect. Consistently, we found a weak but significant correlation ( p = 0.013) between the frequency of the S/S genotype and severity of withdrawal symptoms (WDS): no WOS [18.3%, odds ratio (OR) = 1.16], vegetative WDS only (21.8%, OR = 1.44), and severe WDS with either withdrawal seizure only or delirium only (25.0%, OR = 1.69), and both withdrawal seizure and delirium (30.8%, OR = 2.30). Further studies are required to test whether the tentative genotype-phenotype relationship occurred by chance or reflects a real genotypic association between a recessively modifying effect of the short variant of the functional 5-HTT promoter polymorphism and alcohol withdrawal vulnerability.     

5-HT在肠易激综合征发病机制中的研究现状

肠易激综合征（IBS）是常见的功能性胃肠病之一,其发生与5-羟色胺（5-HT）统的功能改变密切相关。5-HT系统功能改变通常包括5-HT受体及其亚型、5-HT转运体（SERT）其多态性等改变,参与调节胃肠道感觉、运动、分泌等功能,并与精神心理活动异常密切相关。本文就5-HT在IBS发病机制中的研究现状作一综述。