基于脑肠交互机制探讨肠道微生物调节IBS-D内脏高敏的研究进展
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摘要
腹泻型肠易激综合征(IBS-D)是一种生物心理社会病,也是一种多因素相互作用引起的慢性功能性肠病。IBSD的发病与内脏感觉异常、肠道动力学异常、肠黏膜微炎性反应、遗传、饮食不耐受等多种因素有关,其中内脏高敏是IBS-D主要的病理生理机制之一,是一种不明原因出现的肠道对寒冷、不良情绪等刺激因素高度敏感的病理过程,但内脏高敏发生机制尚未完全阐明。IBS-D的发病与脑肠互动功能紊乱密切相关,IBS-D患者由于病情反复常常伴随焦虑、抑郁等精神症状,而长期慢性精神应激易诱发及加重IBS-D内脏高敏状态。脑源性神经营养因子(BDNF)及其高亲和受体络氨酸激酶B(Trk B)是研究脑肠互动神经环路的热点,BDNF于中枢神经系统和胃肠道上大量表达,能促进神经系统的发育,维持成熟神经细胞的正常功能,还能调节胃肠道动力和内脏敏感性,是引起和导致神经疼痛敏感的重要细胞因子。肠道微生物是脑肠互动的关键纽带,人精神异常与肠道微生物环境改变引发的肠道症状密切关联。反复精神刺激(如抑郁、焦虑等)可导致肠道菌群的改变,另一方面,肠道菌群结构的改变与神经系统的发育和大脑的功能密切相关。本文以肠道微生物为切入点,以脑—肠轴为轴线,基于BDNF/Trk B通路,探讨肠道菌群调节IBS-D内脏高敏机制的相关性研究。
Diarrhea-predominant irritable bowel syndrome( IBS-D) is not only a biological mental disorder,but also a kind of chronic functional bowel disease induced by many factors. The pathogenesis of IBS-D is related to visceral sensory abnormalities,intestinal dynamics abnormalities,intestinal mucosal micro-inflammatory reactions,heredity, dietary intolerance and other factors. The visceral hypersensitivity is one of the main pathophysiology,and refers to an unknown cause of intestinal hypersensitivity to cold,bad mood and other stimuli.However,its mechanism remains unclear. The pathogenesis of IBS-D is closely related to the disturbance of brain and intestinal interaction. IBS-D patients often suffer from anxiety,depression and other psychiatric symptoms due to repeated illness,but long-term chronic mental stress can induce and aggravate IBS-D visceral hypersensitivity.Brain-derived neurotrophic factor( BDNF) and its high-affinity receptor tyrosine kinase B( TrkB) are hotspots in studies about brain-gut axis. BDNF is a highly expressed cytokine in the central nervous system and gastrointestinal tract,and can promote the development of the nervous system,maintain the normal function of mature nerve cells and regulate the gastrointestinal motility and visceral sensitivity. Intestinal microbiota is the key link of brain-gut interaction. Mental disorders are closely related to intestinal symptoms caused by changes in intestinal microbial environment. Repeated mental stimulation can lead to changes in intestinal flora; on the other hand,changes in intestinal flora structure are closely related to the development of the nervous system and the function of the brain.With intestinal microbiota as the study object,this article mainly discusses the effect of intestinal microbiota in regulating visceral hypersensitivity of IBS-D based on brain-gut axis( BDNF/TrkB signaling pathway).
Diarrhea-predominant irritable bowel syndrome( IBS-D) is not only a biological mental disorder,but also a kind of chronic functional bowel disease induced by many factors. The pathogenesis of IBS-D is related to visceral sensory abnormalities,intestinal dynamics abnormalities,intestinal mucosal micro-inflammatory reactions,heredity, dietary intolerance and other factors. The visceral hypersensitivity is one of the main pathophysiology,and refers to an unknown cause of intestinal hypersensitivity to cold,bad mood and other stimuli.However,its mechanism remains unclear. The pathogenesis of IBS-D is closely related to the disturbance of brain and intestinal interaction. IBS-D patients often suffer from anxiety,depression and other psychiatric symptoms due to repeated illness,but long-term chronic mental stress can induce and aggravate IBS-D visceral hypersensitivity.Brain-derived neurotrophic factor( BDNF) and its high-affinity receptor tyrosine kinase B( TrkB) are hotspots in studies about brain-gut axis. BDNF is a highly expressed cytokine in the central nervous system and gastrointestinal tract,and can promote the development of the nervous system,maintain the normal function of mature nerve cells and regulate the gastrointestinal motility and visceral sensitivity. Intestinal microbiota is the key link of brain-gut interaction. Mental disorders are closely related to intestinal symptoms caused by changes in intestinal microbial environment. Repeated mental stimulation can lead to changes in intestinal flora; on the other hand,changes in intestinal flora structure are closely related to the development of the nervous system and the function of the brain.With intestinal microbiota as the study object,this article mainly discusses the effect of intestinal microbiota in regulating visceral hypersensitivity of IBS-D based on brain-gut axis( BDNF/TrkB signaling pathway).
引文
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[11]梁瑞峰,葛文静,王慧森,等.痛泻要方加减引经药防风对肠易激综合征大鼠内脏敏感性及脑肠轴不同靶点脑肠肽的影响[J].中国实验方剂学杂志,2018,24(2):152-157.
[12]晁冠群,吕宾,孟立娜,等.痛泻要方对内脏高敏感大鼠脑、脊髓CRF表达的影响[J].中国中药杂志,2010,35(15):2012-2016.
[13]魏睦新,吴燕敏,刘振清,等.痛泻要方组成药物对大鼠结肠平滑肌运动的影响及机制[J].中国实验方剂学杂志,2010,16(8):131-134.
[14]谭许朋,韩宗余,温亚,等.痛泻要方及防风对肠上皮Caco2细胞屏障功能的影响[J].深圳中西医结合杂志,2014,24(10):1-3.
[15]余萍.基于BDNF-TrkB信号通路研究痛泻要方中白芍防风缓解IBS-D内脏高敏的作用机制[D].成都:成都中医药大学,2016.
[16]李媛.腹泻型、便秘型以及混合型肠易激综合征患者肠道菌群的差异性比较[J].世界最新医学信息文摘,2018,18(46):61-62.
[17]欧枢,贾玉杰.肠道菌群失衡诱发肠易激综合征的机制[J].中国微生态学杂志,2017,29(6):742-745.
[18]赖淑媚,王立生.肠道菌群失调与肠易激综合征关系的研究进展[J].当代医学,2018,24(3):182-184.
[19]刘靖.痛泻要方治疗腹泻型肠易激综合征的疗效观察及其对肠道菌群的影响[D].北京:中国中医科学院,2017.
[20]Fridrich M J. Unraveling the influence of gut microbrs on the mind[J]. JAMA,2015,313(17):1699-1701.
[21]ZHOU Q,Verne G N. New insights into visceral hypersensitivity-clinical implications in IBS[J]. Nat Rev Gastroenterol Hepatol,2011,8(6):349-355.
[22]Lembo A J,Lacy B E,Zuckerman M J,et al. Eluxadoline for irritable bowel syndrome with diarrhea[J]. New Engl J Med,2016,374(3):242-253.
[23]刘萍,罗本燕.肠道微生态与中枢神经系统疾病的相关性[J].中国神经精神疾病杂志,2016,42(4):251-254.
[24]Fukudo S,Nomura T,Muranaka M,et al. Brain-gut response to stress and cholinergic stimulation in irritable bowel syndrome. A preliminary study[J]. J Clin Gastroenterol,1993,17(2):133-141.
[25]焦黛妍,孙建华.脑源性神经营养因子在肠道高敏感中的研究进展[J].胃肠病学,2014,19(2):121-123.
[26]Lim J Y,Park S I,Oh J H,et al. Brain-derived neurotrophic factor stimulates the neural differentiation of human umbilical cord blood-derived mesenchymal stem cells and survival of differentiated cells through MAPK/ERK and PI3K/Akt-dependent signaling pathways[J].J Neurosci Res,2008,86(10):2168-2178.
[27]ZHENG Z,ZENG Y,YANG W,et al. Irritable bowel syndrome may be induced by decreased neuroplasticity[J]. Neuro Endocrinol Lett,2014,35(8):655-665.
[28]YU Y B,ZUO X L,ZHAO Q J,et al. Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome[J]. Gut,2012,61(5):685-694.
[29]董智瑀,许树长.脑源性神经营养因子介导精神应激诱发内脏高敏感的研究进展[J].外科研究与新技术,2017,6(3):209-211.
[30]陈飞雪,李延青.脑源性神经营养因子对肠道感觉调节作用的研究[J].胃肠病学和肝病学杂志,2011,20(3):287-290.
[31]Coull J A,Beggs S,Boudreau D,et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain[J]. Nature,2005,438(7070):1017-1021.
[32]Obata K,Noguchi K. BDNF in sensory,neurons and chronic pain[J]. Neurosci Res,2006,55(1):1-10.
[33]梁超,徐斌.脑源性神经营养因子在肠道中作用的研究进展[J].世界华人消化杂志,2015,23(25):5649-5654.
[34]Lommatzsch M,Braun A,Mannsfeldt A,et al. Abundant production of brain-derived neurotrophic factor by visceral epithelia. Implications for paracrine and targetderived neurotrophic functions[J]. Am J Pathol,1999,155(4):1183-1193.
[35]LI F,ZHANG J W,WEI R,et al. Sex-differential modulation of visceral pain by brain derived neurotrophic factor(BDNF)in rats[J]. Neurosci Lett,2010,478(3):184-187.
[36]安荣.基于“脑肠菌轴”探讨痛泻要方治疗IBS模型大鼠新机制[D]成都:成都中医药大学,2016.
[37]Saulnier D M, Rehle K, Mistretta T A, et al.Gastrointestinal micro biome signatures of pediatric pediatric patients with irritable bowel syndrome[J].Gastronenterology,2011,141(5):1782-1791.
[38]胡乐义,王巧民,姜彬言,等.肠易激综合征患者肠道菌群的变化及意义[J].安徽医科大学学报,2012,47(1):86-89.
[39]陈志华,张凤梅.不同亚型肠易激综合征病人的肠道菌群状况研究[J].江西医药,2014,49(12):1459-1461.
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