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。     

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.     

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.     

Epidermal growth factor upregulates serotonin transporter and its association with visceral hypersensitivity in irritable bowel syndrome

AIM: To investigate the role of epidermal growth factor (EGF) in visceral hypersensitivity and its effect on the serotonin transporter (SERT).METHODS: A rat model for visceral hypersensitivity was established by intra-colonic infusion of 0.5% acetic acid in 10-d-old Sprague-Dawley rats. The visceral sensitivity was assessed by observing the abdominal withdrawal reflex and recording electromyographic activity of the external oblique muscle in response to colorectal distension. An enzyme-linked immunosorbent assay was used to measure the EGF levels in plasma and colonic tissues. SERT mRNA expression was detected by real-time PCR while protein level was determined by Western blot. The correlation between EGF and SERT levels in colon tissues was analyzed by Pearson’s correlation analysis. SERT function was examined by tritiated serotonin (5-HT) uptake experiments. Rat intestinal epithelial cells (IEC-6) were used to examine the EGF regulatory effect on SERT expression and function via the EGF receptor (EGFR).RESULTS: EGF levels were significantly lower in the rats with visceral hypersensitivity as measured in plasma (2.639 ± 0.107 ng/mL vs 4.066 ± 0.573 ng/mL, P < 0.01) and in colonic tissue (3.244 ± 0.135 ng/100 mg vs 3.582 ± 0.197 ng/100 mg colon tissue, P < 0.01) compared with controls. Moreover, the EGF levels were positively correlated with SERT levels (r = 0.820, P < 0.01). EGF displayed dose- and time-dependent increased SERT gene expressions in IEC-6 cells. An EGFR kinase inhibitor inhibited the effect of EGF on SERT gene upregulation. SERT activity was enhanced following treatment with EGF (592.908 ± 31.515 fmol/min per milligram vs 316.789 ± 85.652 fmol/min per milligram protein, P < 0.05) and blocked by the EGFR kinase inhibitor in IEC-6 cells (590.274 ± 25.954 fmol/min per milligram vs 367.834 ± 120.307 fmol/min per milligram protein, P < 0.05).CONCLUSION: A decrease in EGF levels may contribute to the formation of visceral hypersensitivity through downregulation of SERT-mediated 5-HT uptake into enterocytes.     

肠易激综合征患者小肠黏膜5-HT信号系统的研究

目的探讨肠易激综合征（IBS）患者不同部位小肠黏膜5-羟色胺（5-HT）水平及肠嗜铬细胞（EC细胞）数量是否改变。方法选取24例便秘型IBS（IBS-C）、26例腹泻型IBS（IBS-D）患者和26名健康人,行小肠镜及结肠镜检查并取十二指肠降段、近端空肠和回肠末段黏膜,用高压液相色谱-电化学法和免疫组织化学检测5-HT含量和EC细胞。结果IBSC患者近端空肠黏膜的5-HT含量与健康人相比有统计学意义（122±54ng／mg蛋白比188±91ng／mg蛋白,P〈0．05）,而十二指肠降段和回肠末段黏膜5-HT含量（182±90ng／mg蛋白、61±35ng／mg蛋白）与健康人相比（256±84ng／mg蛋白、93±45ng／mg蛋白）无统计学意义（P〉0．05）。IBS-D患者不同部位小肠黏膜5-HT含量与健康人相比均无统计学意义（P〉0．05）。IBS-C和IBSD患者不同部位小肠黏膜EC细胞数量与健康人相比均无统计学意义（P〉0．05）。结论上述结果提示1BS患者小肠黏膜5HT信号系统异常是其发病机制之-,但是在IBS-C和IBS-D之间有差异。     

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.     

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。     

5-羟色胺转运体表达与肠易激综合征躯体及心理症状的相关性

目的 研究5-羟色胺转运体(SERT) mRNA及蛋白表达水平与肠易激综合征(IBS)患者躯体和心理症状的相关性.方法 选取消化科门诊IBS患者254例为病例组,健康体检者及志愿者120名为对照组.采用实时定量PCR检测SERT mRNA,Western印迹分析检测SERT的蛋白表达量,应用精神心理症状自评量表(SCL-90)评测研究对象,探讨SERT蛋白表达与心理症状之间的相关性.结果 便秘型肠易激综合征(C-IBS)95例,腹泻型肠易激综合征(D-IBS)116例,交替型肠易激综合征(A-IBS)43例.C-IBS组SERT mRNA及蛋白表达(0.58±0.24;0.99±0.51)显著高于A-IBS组(0.37±0.22;0.67±0.34)、D-IBS组(0.41±0.26;0.71±0.41)和对照组(0.42±0.29;0.78±0.47)(均数差异=0.21、0.17、0.16,均P＜0.01;均数差异=0.31、0.27、0.21,均P＜0.05),A-IBS组与D-IBS组间比较差异无统计学意义(P＞0.05).SERT蛋白表达量与躯体化症状(r=-0.67,P＜0.01)、抑郁因子(r=-0.81,P＜0.01)、焦虑因子(r=-0.72,P＜0.01)和敌对因子呈负相关(r=-0.66,P＜0.01),与人际关系敏感、强迫症状、恐惧、偏执和精神病因子均不存在相关性(P＞0.05).结论 结肠黏膜SERT mRNA及蛋白的水平与IBS患者的躯体及心理症状相关,患者SERT mRNA及蛋白表达越多越容易出现便秘症状,而SERT蛋白含量越少越容易出现躯体化、焦虑、抑郁和敌对的情绪表现.     

Low-grade inflammation plays a pivotal role in gastrointestinal dysfunction in irritable bowel syndrome

The pathogenesis of irritable bowel syndrome (IBS) is considered to be multifactorial and includes psychosocial factors, visceral hypersensitivity, infection, microbiota and immune activation. It is becoming increasingly clear that low-grade inflammation is present in IBS patients and a number of biomarkers have emerged. This review describes the evidence for low-grade inflammation in IBS and explores its mechanism with particular focus on gastrointestinal motor dysfunction. Understanding of the immunological basis of the altered gastrointestinal motor function in IBS may lead to new therapeutic strategies for IBS.     

肥大细胞在肠易激综合征发病机制中的研究进展

肠易激综合征(irritable bowel syndrome,IBS)是以腹痛、腹部不适伴排便习惯改变和/或大便性状异常为特征的常见功能性胃肠病.IBS全球患病率为2%-15%.本病病因及发病机制尚不十分明确,目前认为多与胃肠动力异常、内脏高敏、感染与炎症、神经-内分泌失调、精神心理、食物过敏等多种因素有关.近年来提出的"神经-免疫-内分泌网络"理论在IBS发病机制中占有重要地位.研究发现,胃肠道的肥大细胞(mast cells,MCs)在IBS的发病中发挥着重要作用.本文拟以MCs在IBS中的发病机制的最新研究进展作一综述.     

肠易激综合征流行病学研究现状与进展

肠易激综合征(irritable bowel syndrome,IBS)是一种以慢性或者反复发作的腹痛伴排便习惯改变为特征的功能性肠病,并缺乏形态学和生化标志的异常。IBS是一种全球性疾病,人群患病率较高,其症状可反复发作,严重影响患者的生活质量,并占用了大量的医疗资源。IBS的病因和发病机制尚未明了,随着对IBS认识的不断深入和发展,国内外在不同时期,采用不同的标准和方法,对IBS的流行病学进行了较深入的研究,但不同国家和地区、不同人群的IBS患病率及其分布特征研究结果不尽相同,影响IBS的危险因素主要包括社会心理因素及遗传、感染、食物、药物因素等,现就近年来国内外IBS流行病学的研究情况作一综述。     

State-of-the-art of irritable bowel syndrome and inflammatory bowel disease research in 2008

Irritable bowel syndrome （IBS） and inflammatory bowel disease （IBD） are two of the leading causes of chronic intestinal conditions in the world. This issue of World Journal of Gastroenterology （ WJG） presents a series of papers from world experts who discuss the current knowledge and opinions on these important conditions. Although great strides have been made in the diagnosis, treatment and pathology of IBS and IBD; much has yet to be explained. The etiologies and risk factors of these multifactorial conditions remain elusive. Specific diagnostic biomarkers need to be developed and safer treatments developed. The burden of IBS and IBD on the healthcare system is felt with repeated medical care visits and high costs. IBS and IBD patients can account for 30%-50% of office visits at gastroenterology services/clinics. Over one million people have IBD in the United States, with 30000 new cases being diagnosed every year. One-quarter million people in the UK are afflicted with IBD. The cost of medical care in the United States for IBD is estimated to be $1.8 billion/year.