白　濤　宋　軍　侯曉華

華中科技大學(xué)同濟醫(yī)學(xué)院附屬協(xié)和醫(yī)院消化科(430022)

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·綜述·

神經(jīng)調(diào)控通路在腸易激綜合征內(nèi)臟高敏感發(fā)病機制中作用的研究進展*

白濤宋軍侯曉華#

華中科技大學(xué)同濟醫(yī)學(xué)院附屬協(xié)和醫(yī)院消化科(430022)

摘要腸易激綜合征(IBS)是臨床最常見的功能性胃腸病之一，影響患者生活質(zhì)量，給患者日常生活、心理健康帶來沉重負擔。諸多研究顯示內(nèi)臟高敏感(VHS)是IBS發(fā)病的重要病理生理機制之一，神經(jīng)調(diào)控在VHS發(fā)生中起關(guān)鍵作用。本文就神經(jīng)調(diào)控通路在IBS VHS發(fā)病機制中作用的研究進展作一綜述。

關(guān)鍵詞腸易激綜合征；內(nèi)臟高敏感性；功能性胃腸?。恢袠猩窠?jīng)系統(tǒng)；周圍神經(jīng)系統(tǒng)

Central Nervous System;Peripheral Nervous System

腸易激綜合征(irritable bowel syndrome, IBS)是臨床最常見的功能性胃腸病(functional gastrointestinal disorders, FGIDs)之一，全球發(fā)病率為9%～23%，嚴重影響患者生活質(zhì)量，給患者日常生活、心理健康帶來沉重負擔，但其發(fā)病機制仍未完全明確[1]。諸多研究顯示內(nèi)臟高敏感(visceral hypersensitivity, VHS)是IBS發(fā)病的重要病理生理機制之一，神經(jīng)調(diào)控在VHS發(fā)生中起關(guān)鍵作用。本文就神經(jīng)調(diào)控通路在IBS VHS發(fā)病機制中作用的研究進展作一綜述。

一、VHS與IBS

VHS指內(nèi)臟感覺閾值降低，主要表現(xiàn)為對刺激的感受性增強，即對低于生理性刺激強度的刺激即感不適，對生理性刺激感到疼痛或不適，對傷害性刺激的感覺閾值降低。研究[2]指出，30%～50%的FGIDs患者存在VHS，而無胃腸道運動異常，VHS與IBS患者癥狀密切相關(guān)。IBS患者初始感覺閾值、初始排便感覺閾值、排便窘迫閾值或不舒適感閾值、最大忍受閾值或疼痛閾值明顯低于健康志愿者[3-4]。給予結(jié)直腸擴張刺激后，通過功能性磁共振成像(fMRI)觀察，發(fā)現(xiàn)IBS VHS患者的中樞痛覺相關(guān)腦區(qū)功能更為活躍[5-6]。此外，通過基因敲除/自發(fā)VHS模型、應(yīng)激模型、炎癥后模型等IBS動物模型亦證實了IBS病理過程中存在VHS，并為VHS的機制研究提供了支持[7]。

二、VHS發(fā)生的機制

1. VHS發(fā)生的神經(jīng)解剖學(xué)基礎(chǔ)：內(nèi)臟痛覺轉(zhuǎn)導(dǎo)通路包含三級神經(jīng)元。Ⅰ級神經(jīng)元胞體位于背根神經(jīng)節(jié)，感受外周感受器刺激信號后，將信號傳遞至脊髓背角神經(jīng)元(Ⅱ級神經(jīng)元)，經(jīng)脊髓丘腦束、脊髓網(wǎng)狀束上傳至丘腦和網(wǎng)狀結(jié)構(gòu)的Ⅲ級神經(jīng)元，再投射至軀體感覺皮質(zhì)、扣帶回前皮質(zhì)等結(jié)構(gòu)，產(chǎn)生內(nèi)臟痛覺。此外，丘腦通過下行抑制系統(tǒng)作用于脊髓背角神經(jīng)元易化或抑制內(nèi)臟感覺信號的處理。因此，外周刺激、中樞轉(zhuǎn)導(dǎo)通路、中樞信號處理及其相互作用等多水平共同調(diào)節(jié)內(nèi)臟敏感性。

2. VHS發(fā)生的中樞機制：應(yīng)用fMRI和正電子發(fā)射型計算機斷層顯像(PET)研究[8]發(fā)現(xiàn)，給予直腸擴張刺激后，IBS母嬰分離模型大鼠前扣帶回、前部額葉、島葉、海馬、丘腦、杏仁核、下丘腦等區(qū)域功能活動增強，抗傷害性感受的導(dǎo)水管周圍灰質(zhì)活動性降低。上述與痛覺相關(guān)的中樞核團功能活動改變提示中樞神經(jīng)系統(tǒng)的活化參與IBS VHS的形成。

中樞敏感性增強是VHS發(fā)生的重要原因之一。外周刺激可使中樞神經(jīng)元興奮性持續(xù)增強，包括脊髓神經(jīng)元和脊髓水平以上的神經(jīng)元動作電位誘發(fā)閾值降低、神經(jīng)元反應(yīng)性增強、脊髓神經(jīng)元感受野擴大，引起傳入中樞神經(jīng)系統(tǒng)的信號增加，繼而改變生物活性物質(zhì)的釋放。Chen等[9]通過動物實驗研究發(fā)現(xiàn)，結(jié)直腸擴張刺激可使IBS模型大鼠海馬CA1區(qū)長時程增強效應(yīng)增加，通過電生理和在鞘內(nèi)注射抑制劑證明，N-甲基-D-天冬氨酸受體2B亞基(NR2B)參與CA1區(qū)長時程增強效應(yīng)，與IBS VHS形成有關(guān)。Jia等[10]對IBS模型大鼠研究發(fā)現(xiàn)，下丘腦室旁核中的多肽nesfatin-1可能與IBS發(fā)生VHS相關(guān)，nesfatin-1可能通過作用于促腎上腺皮質(zhì)激素釋放因子(CRF)/CRF受體1通路，并增加CRF神經(jīng)元胞質(zhì)鈣離子濃度，從而介導(dǎo)VHS發(fā)生。Tran等[11]的研究發(fā)現(xiàn)，組蛋白去乙?；种苿┛蓽p輕IBS模型大鼠VHS，進一步研究顯示，大鼠體內(nèi)參與疼痛處理的杏仁核存在CRF和糖皮質(zhì)激素受體(glucocorticoid receptor, GR)基因甲基化改變，提示表觀遺傳學(xué)機制在慢性應(yīng)激IBS模型大鼠VHS發(fā)病機制中發(fā)揮重要作用。上述研究顯示中樞調(diào)控在VHS的發(fā)生中起重要作用，但相關(guān)機制仍需進一步研究。

3. VHS發(fā)生的脊髓機制：脊髓背角是外周刺激沿腦-腸軸傳入高級中樞的中繼站。內(nèi)臟感覺信號經(jīng)內(nèi)臟感覺傳入神經(jīng)傳遞至位于脊髓背根神經(jīng)節(jié)的神經(jīng)元胞體后交叉至對側(cè)，上行傳輸至大腦皮層產(chǎn)生內(nèi)臟感覺。內(nèi)臟感覺主要通過脊髓背角傳遞至中樞，VHS發(fā)生時，外周刺激脊髓背角神經(jīng)元釋放多種神經(jīng)遞質(zhì)和神經(jīng)調(diào)質(zhì)，激活配體門控離子通道，使脊髓背角神經(jīng)元持續(xù)活化，從而使脊髓致敏。

Luo等[12]的研究發(fā)現(xiàn)，NR2B受酪氨酸激酶調(diào)節(jié)，其活化可增加結(jié)腸對機械擴張刺激的敏感性，提示脊髓水平N-甲基-D-天冬氨酸(NMDA)受體的調(diào)控可能是VHS發(fā)生的重要機制。脊髓水平去甲腎上腺素(NE)在IBS VHS發(fā)生中亦起著重要作用。Zhang等[13]對應(yīng)激制備的IBS模型大鼠研究發(fā)現(xiàn)，應(yīng)激時大鼠血漿NE水平增加，后者可活化背根神經(jīng)節(jié)中的β2腎上腺素受體，參與VHS的發(fā)生。β2腎上腺素受體拮抗劑可降低VHS，并呈劑量依賴性，而β1和β3腎上腺素受體拮抗劑無此作用。電生理實驗證實，選擇性β2腎上腺素受體拮抗劑可降低結(jié)腸特異性背根神經(jīng)節(jié)的興奮性。此外，腦源性神經(jīng)營養(yǎng)因子(brain-derived neurotrophic factor, BDNF)、神經(jīng)生長因子(nerve growth factor, NGF)、TLR4/MyD88/NF-κB信號通路的激活等亦是參與VHS發(fā)生的重要機制[14-16]。

脊髓水平離子通道蛋白表達和功能的改變亦是IBS中VHS發(fā)生的重要機制。研究[15,17]顯示，IBS模型大鼠背根神經(jīng)節(jié)中Nav1.8通道和酸敏感離子通道表達受到調(diào)控，從而介導(dǎo)VHS發(fā)生。Zhou等[18]的研究顯示，在動物模型中，VHS的發(fā)生與辣椒素受體1(transient receptor potential vanilloid 1，TRPV1)通路相關(guān)，上調(diào)miRNA-199表達可抑制TRPV1通路，降低內(nèi)臟敏感性。

4. VHS的外周機制：外周刺激經(jīng)末梢終止于肌肉、黏膜、漿膜的初級傳入神經(jīng)元傳入后，進一步在脊髓背角交換神經(jīng)元上傳至中樞。腸神經(jīng)系統(tǒng)(enteric nervous system, ENS)具有結(jié)構(gòu)和功能的可塑性，是VHS形成的基礎(chǔ)。外周和中樞的致敏因素可引起胃腸道生物活性物質(zhì)釋放，繼而改變受體表達和信號通路活化，調(diào)節(jié)ENS的神經(jīng)可塑性，從而導(dǎo)致VHS發(fā)生。

研究顯示，在VHS發(fā)生過程中，腸道信號分子分泌改變。內(nèi)源性信號分子如交感神經(jīng)末梢和腸嗜鉻細胞分泌的NE、5-羥色胺(5-HT)、組胺、三磷酸腺苷(ATP)、NGF等，可直接刺激內(nèi)臟傳入末梢，與受體結(jié)合后誘導(dǎo)傳入神經(jīng)元離子通道開放，在外周致敏中發(fā)揮重要作用[19-20]。如5-HT作為重要的神經(jīng)遞質(zhì)和調(diào)質(zhì)，其合成、釋放以及再攝取與VHS密切相關(guān)[21-24]；鳥苷酸環(huán)化酶C(GC-C)激動劑在動物模型中對VHS有治療效果[25]。

Buckley等[26]對IBS模型大鼠的研究發(fā)現(xiàn)，干預(yù)白細胞介素-6和CRF1受體表達可降低結(jié)腸VHS，并伴隨VHS相關(guān)Cav3.2通道和胞內(nèi)信號分子STAT3、SOCS3以及ERK1/2表達發(fā)生改變。此外，胰高血糖素樣肽1[27]、大麻素受體2[28]、血清素轉(zhuǎn)運體[29]等受體功能的調(diào)控亦參與了VHS形成，在外周致敏中起重要作用。

腸系膜傳入神經(jīng)調(diào)控在VHS發(fā)生中亦起關(guān)鍵作用。研究[30-31]顯示，在旋毛蟲制備的感染后IBS(PI-IBS)模型中，豚鼠腸系膜神經(jīng)自發(fā)性電活動增加，對壓力和酸的刺激反應(yīng)明顯增強，與VHS相關(guān)，提示腸系膜神經(jīng)高敏感在VHS的發(fā)生中發(fā)揮重要作用。

三、改變VHS神經(jīng)調(diào)控通路的誘因

在IBS VHS發(fā)生過程中，多種因素參與誘導(dǎo)神經(jīng)調(diào)控通路的改變，其中包括精神心理因素、腸道炎癥與免疫狀態(tài)改變、腸道微生態(tài)改變、食物不耐受等。

1. 精神心理因素：精神心理應(yīng)激，如早期生活事件可導(dǎo)致持續(xù)的應(yīng)激反應(yīng)，促進IBS VHS發(fā)生，其機制可能包括引起NGF介導(dǎo)脊髓神經(jīng)可塑性發(fā)生改變、腸道5-HT通路改變以及中樞痛覺環(huán)路激活[32]。精神心理因素的影響在臨床和基礎(chǔ)研究中均被證實參與IBS VHS的發(fā)生，母嬰分離、應(yīng)激等多種應(yīng)激模型可成功模擬IBS VHS的癥狀[33]。

2. 腸道炎癥與免疫狀態(tài)改變：目前認為腸道局部免疫紊亂是誘發(fā)VHS的重要因素之一。感染、腸道免疫性疾病等患者均可出現(xiàn)VHS癥狀。旋毛蟲感染、應(yīng)激因素刺激以及化學(xué)物質(zhì)誘導(dǎo)損傷等動物造模方法被廣泛應(yīng)用于IBS VHS的研究。感染或炎癥導(dǎo)致腸神經(jīng)受損，在存留的肌間神經(jīng)叢和黏膜下神經(jīng)叢中，內(nèi)在感覺神經(jīng)元興奮性增加，突觸傳遞發(fā)生改變，這些改變在感染后可持續(xù)存在[33]。此外，Hughes等[34]的研究發(fā)現(xiàn)，IBS患者結(jié)腸固有層單核巨噬細胞數(shù)量減少，引起β-內(nèi)啡肽分泌量降低，導(dǎo)致結(jié)腸傳入神經(jīng)末梢傳入增加，參與形成VHS。Carroll等[35]的研究顯示，肥大細胞的數(shù)量和種類在VHS模型大鼠與正常對照大鼠間存在明顯差異，肥大細胞穩(wěn)定劑可降低IBS模型大鼠的VHS，提示肥大細胞參與VHS形成。Song等[30]的研究發(fā)現(xiàn)，PI-IBS 大鼠腸道肥大細胞數(shù)量增加，腸道傳入神經(jīng)放電頻率增加，肥大細胞穩(wěn)定劑可抑制感染后腸傳入神經(jīng)放電頻率的改變，提示肥大細胞參與IBS感覺功能的調(diào)節(jié)。

3. 腸道微生態(tài)改變：近年研究發(fā)現(xiàn)腸道微生態(tài)與腸道疾病密切相關(guān)。Crouzet等[36]的研究發(fā)現(xiàn)，無菌大鼠移植IBS患者糞便菌群后，可出現(xiàn)VHS癥狀，提示腸道微生物參與IBS內(nèi)臟敏感性的調(diào)節(jié)。Wang等[37]的研究表明，益生菌治療可降低PI-IBS模型小鼠的內(nèi)臟敏感性。此外，有臨床研究證實，作用于局部腸道的抗菌藥物利福昔明可緩解IBS相關(guān)癥狀[38]。推測腸道微生物可能以多種機制協(xié)同調(diào)節(jié)VHS，包括改善腸黏膜炎癥反應(yīng)、維持腸道上皮通透性等。

4. 食物不耐受：飲食可能是誘發(fā)VHS的重要因素。部分IBS患者存在食物不耐受，主要包括牛奶、小麥、蛋類等。食物不耐受可能通過腸道IgE或IgG免疫反應(yīng)參與VHS發(fā)生[39]，具體機制有待進一步研究。

四、結(jié)語

綜上所述， VHS是IBS發(fā)病的重要機制之一，由外周刺激、中樞轉(zhuǎn)導(dǎo)通路、中樞信號處理及其相互作用而產(chǎn)生，與應(yīng)激、腸道免疫、腸道微生態(tài)、食物等因素有關(guān)。對VHS發(fā)生機制中神經(jīng)調(diào)控通路的研究將進一步明確IBS的發(fā)病機制，從而為治療提供有效靶點。

參考文獻

1 Saha L. Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine[J]. World J Gastroenterol, 2014, 20 (22): 6759-6773.

2 陳艷，劉詩. 功能性胃腸病的最新研究新進展[J]. 臨床消化病雜志, 2012, 24 (6): 367-370.

3 T?rnblom H, Van Oudenhove L, Tack J, et al. Interaction between preprandial and postprandial rectal sensory and motor abnormalities in IBS[J]. Gut, 2014, 63 (9): 1441-1449.

4 Liu L, Liu BN, Chen S, et al. Visceral and somatic hypersensitivity, autonomic cardiovascular dysfunction and low-grade inflammation in a subset of irritable bowel syndrome patients[J]. J Zhejiang Univ Sci B, 2014, 15 (10): 907-914.

5 Larsson MB, Tillisch K, Craig AD, et al. Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome[J]. Gastroenterology, 2012, 142 (3): 463-472.

6 Lowén MB, Mayer E, Tillisch K, et al. Deficient habituation to repeated rectal distensions in irritable bowel syndrome patients with visceral hypersensitivity[J]. Neurogastroenterol Motil, 2015, 27 (5): 646-655.

7 Greenwood-Van Meerveld B, Prusator DK, Johnson AC. Animal models of gastrointestinal and liver diseases. Animal models of visceral pain: pathophysiology, translational relevance, and challenges[J]. Am J Physiol Gastrointest Liver Physiol, 2015, 308 (11): G885-G903.

8 Wouters MM, Van Wanrooy S, Casteels C, et al. Altered brain activation to colorectal distention in visceral hypersensitive maternal-separated rats[J]. Neurogastroenterol Motil, 2012, 24 (7): 678-685, e297.

9 Chen Y, Chen AQ, Luo XQ, et al. Hippocampal NR2B-containing NMDA receptors enhance long-term potentiation in rats with chronic visceral pain[J]. Brain Res, 2014, 1570: 43-53.

10Jia FY, Li XL, Li TN, et al. Role of nesfatin-1 in a rat model of visceral hypersensitivity[J]. World J Gastroenterol, 2013, 19 (22): 3487-3493.

11Tran L, Chaloner A, Sawalha AH, et al. Importance of epigenetic mechanisms in visceral pain induced by chronic water avoidance stress[J]. Psychoneuroendocrinology, 2013, 38 (6): 898-906.

12Luo XQ, Cai QY, Chen Y, et al. Tyrosine phosphorylation of the NR2B subunit of the NMDA receptor in the spinal cord contributes to chronic visceral pain in rats[J]. Brain Res, 2014, 1542: 167-175.

13Zhang C, Rui YY, Zhou YY, et al. Adrenergic β2-receptors mediates visceral hypersensitivity induced by heterotypic intermittent stress in rats[J]. PLoS One, 2014, 9 (4): e94726.

14Winston JH, Li Q, Sarna SK. Chronic prenatal stress epigenetically modifies spinal cord BDNF expression to induce sex-specific visceral hypersensitivity in offspring[J]. Neurogastroenterol Motil, 2014, 26 (5): 715-730.

15Matricon J, Muller E, Accarie A, et al. Peripheral contribution of NGF and ASIC1a to colonic hypersensitivity in a rat model of irritable bowel syndrome[J]. Neurogastroenterol Motil, 2013, 25 (11): e740-e754.

16Chen ZY, Zhang XW, Yu L, et al. Spinal toll-like receptor 4-mediated signalling pathway contributes to visceral hypersensitivity induced by neonatal colonic irritation in rats[J]. Eur J Pain, 2015, 19 (2): 176-186.

17Hu S, Xiao Y, Zhu L, et al. Neonatal maternal deprivation sensitizes voltage-gated sodium channel currents in colon-specific dorsal root ganglion neurons in rats[J]. Am J Physiol Gastrointest Liver Physiol, 2013, 304 (4): G311-G321.

18Zhou Q, Yang L, Larson S, et al. Decreased miR-199 augments visceral pain in patients with IBS through translational upregulation of TRPV1[J]. Gut, 2016, 65 (5): 797-805.

19Kirkup AJ, Brunsden AM, Grundy D. Receptors and transmission in the brain-gut axis: potential for novel therapies. Ⅰ. Receptors on visceral afferents[J]. Am J Physiol Gastrointest Liver Physiol, 2001, 280 (5): G787-G794.

20Buéno L, Fioramonti J, Garcia-Villar R. Pathobiology of visceral pain: molecular mechanisms and therapeutic implications. Ⅲ. Visceral afferent pathways: a source of new therapeutic targets for abdominal pain[J]. Am J Physiol Gastrointest Liver Physiol, 2000, 278 (5): G670-G676.

21El-Salhy M, Wendelbo I, Gundersen D. Serotonin and serotonin transporter in the rectum of patients with irritable bowel disease[J]. Mol Med Rep, 2013, 8 (2): 451-455.

22El-Salhy M, Gilja OH, Gundersen D, et al. Endocrine cells in the ileum of patients with irritable bowel syndrome[J]. World J Gastroenterol, 2014, 20 (9): 2383-2391.

23Galligan JJ, Patel BA, Schneider SP, et al. Visceral hypersensitivity in female but not in male serotonin transporter knockout rats[J]. Neurogastroenterol Motil, 2013, 25 (6): e373-e381.

24Gilet M, Eutamene H, Han H, et al. Influence of a new 5-HT4 receptor partial agonist, YKP10811, on visceral hypersensitivity in rats triggered by stress and inflammation[J]. Neurogastroenterol Motil, 2014, 26 (12): 1761-1770.

25Castro J, Harrington AM, Hughes PA, et al. Linaclotide inhibits colonic nociceptors and relieves abdominal pain via guanylate cyclase-C and extracellular cyclic guanosine 3’,5’-monophosphate[J]. Gastroenterology, 2013, 145 (6): 1334-1346.

26Buckley MM, O’Halloran KD, Rae MG, et al. Modulation of enteric neurons by interleukin-6 and corticotropin-releasing factor contributes to visceral hypersensitivity and altered colonic motility in a rat model of irritable bowel syndrome[J]. J Physiol, 2014, 592 (23): 5235-5250.

27Yang Y, Cui X, Chen Y, et al. Exendin-4, an analogue of glucagon-like peptide-1, attenuates hyperalgesia through serotonergic pathways in rats with neonatal colonic sensitivity[J]. J Physiol Pharmacol, 2014, 65 (3): 349-357.

28Iwata Y, Ando K, Taniguchi K, et al. Identification of a highly potent and selective CB2 agonist, RQ-00202730, for the treatment of irritable bowel syndrome[J]. Bioorg Med Chem Lett, 2015, 25 (2): 236-240.

29Qian A, Song D, Li Y, et al. Role of voltage gated Ca2+ channels in rat visceral hypersensitivity change induced by 2,4,6-trinitrobenzene sulfonic acid[J]. Mol Pain, 2013, 9: 15.

30Song J, Zhang L, Bai T, et al. Mast cell-dependent mesenteric afferent activation by mucosal supernatant from different bowel segments of guinea pigs with post-infectious irritable bowel syndrome[J]. J Neurogastroenterol Motil, 2015, 21 (2): 236-246.

31宋軍，楊姣，錢偉等. 感染后腸易激綜合征豚鼠的腸系膜神經(jīng)電活動變化[J]. 中華消化雜志, 2014, 34 (9): 603-606.

32Bian ZX. Novel insights about the mechanism of visceral hypersensitivity in maternally separated rats[J]. Neurogastroenterol Motil, 2012, 24 (7): 593-596.

33Brierley SM, Linden DR. Neuroplasticity and dysfunction after gastrointestinal inflammation[J]. Nat Rev Gastroenterol Hepatol, 2014, 11 (10): 611-627.

34Hughes PA, Moretta M, Lim A, et al. Immune derived opioidergic inhibition of viscerosensory afferents is decreased in irritable bowel syndrome patients[J]. Brain Behav Immun, 2014, 42: 191-203.

35Carroll SY, O’Mahony SM, Grenham S, et al. Disodium cromoglycate reverses colonic visceral hypersensitivity and influences colonic ion transport in a stress-sensitive rat strain[J]. PLoS One, 2013, 8 (12): e84718.

36Crouzet L, Gaultier E, Del’omme C, et al. The hypersensitivity to colonic distension of IBS patients can be transferred to rats through their fecal microbiota[J]. Neurogastroenterol Motil, 2013, 25 (4): e272-e282.

37Wang H, Gong J, Wang W, et al. Are there any different effects ofBifidobacterium,LactobacillusandStreptococcuson intestinal sensation, barrier function and intestinal immunity in PI-IBS mouse model?[J]. PLoS One, 2014, 9 (3): e90153.

38Iorio N, Malik Z, Schey R. Profile of rifaximin and its potential in the treatment of irritable bowel syndrome[J]. Clin Exp Gastroenterol, 2015, 8: 159-167.

39Mansueto P, D’Alcamo A, Seidita A, et al. Food allergy in irritable bowel syndrome: The case of non-celiac wheat sensitivity[J]. World J Gastroenterol, 2015, 21 (23): 7089-7109.

(2015-07-27收稿；2015-08-07修回)

DOI:10.3969/j.issn.1008-7125.2016.06.010

*基金項目：國家自然科學(xué)基金(No.81200271)

Advances in Study on Effect of Neural Regulation Pathway on Pathogenesis of Visceral Hypersensitivity in Irritable Bowel Syndrome

BAITao,SONGJun,HOUXiaohua.

DepartmentofGastroenterology,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan(430022)

Correspondence to: HOU Xiaohua, Email: houxh@medmail.com.cn

AbstractIrritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders, which impacts on patients’ quality of life as well as physical and mental health. Studies have shown that visceral hypersensitivity (VHS) is an important pathophysiological factor in the pathogenesis of IBS, and neural regulation plays a key role in the process of VHS. This article reviewed the advances in study on effect of neural regulation pathway on pathogenesis of VHS in IBS.

Key wordsIrritable Bowel Syndrome;Visceral Hypersensitivity;Functional Gastrointestinal Disorders;

#本文通信作者，Email: houxh@medmail.com.cn