Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome
Brain-derived neurotrophic factor contributes to abdominal pain in irritable bowel syndrome
复制标题
脑源性神经营养因子导致肠易激综合征腹痛
DOI：
10.1136/gutjnl-2011-300265
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发表时间：
2012-05-01
期刊：
影响因子：
24.5
通讯作者：
Li, Yan-Qing
中科院分区：
文献类型：
--
作者：
Yu, Yan-Bo;Zuo, Xiu-Li;Li, Yan-Qing
目的脑源性神经营养因子（BDNF）是神经营养因子家族的一员，可能在多种慢性疼痛中发挥重要作用。本研究探讨了脑源性神经营养因子（BDNF）在肠易激综合征（IBS）患者肠道感觉改变中的作用。方法收集40例符合罗马II标准的IBS患者和21例健康对照者的直肠乙状结肠活检标本。通过经验证的问卷对腹痛进行量化。通过免疫组织化学方法评估粘膜中BDNF和神经纤维的存在。粘膜神经纤维的结构通过透射电子显微镜进行了评估。粘液BDNF的释放通过ELISA测定，并与腹痛评分相关。使用BDNF+/−小鼠进行动物研究，以评估内脏敏感性、粘膜神经纤维密度和超微结构变化。在BDNF+/+小鼠中检测了不同剂量BDNF给药后内脏敏感性和背根神经节中TrkB表达的变化。结果与对照组相比，IBS患者的活检显示BDNF显著上调（p=0.003）。IBS患者的总神经纤维也大幅增加。电子显微镜显示粘膜神经纤维的超微结构损伤（例如，肿胀的线粒体和神经轴突）。BDNF的释放与腹痛评分显著相关。同时，与BDNF+/+小鼠相比，BDNF+/−小鼠对结直肠扩张的腹部退缩反射评分和粘膜蛋白基因产物9.5免疫反应性显著降低。电子显微镜显示BDNF+/−小鼠的粘膜神经纤维发生退行性变化。外源性BDNF可诱导BDNF+/+小鼠背根神经节TrkB表达明显增加，并呈剂量依赖性降低阈压。结论肠易激综合征内脏痛觉过敏可能与肠粘膜BDNF表达增加及肠粘膜神经支配结构改变有关。
Objective Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, may play a critical role in many chronic pain conditions. The possible involvement of BDNF in the altered gut sensation in patients with irritable bowel syndrome (IBS) was investigated in the present study. Methods Rectosigmoid biopsies were collected from 40 patients with IBS fulfilling the Rome II criteria and 21 healthy controls. Abdominal pain was quantified by a validated questionnaire. The presence of BDNF and nerve fibres in the mucosa was assessed by immunohistochemistry. The structure of mucosal nerve fibres was assessed by transmission electron microscopy. Mucosal BDNF release was measured by ELISA and correlated with abdominal pain scores. Animal studies using BDNF+/− mice were carried out to evaluate visceral sensitivity, mucosal nerve fibre density and ultrastructural changes. Alterations of visceral sensitivity and TrkB expression in dorsal root ganglia were examined in BDNF+/+ mice following different doses of BDNF administration. Results Biopsies from patients with IBS revealed a significant upregulation of BDNF (p=0.003), as compared with controls. Total nerve fibres were also substantially increased in patients with IBS. Electron microscopy showed ultrastructural damage on the mucosal nerve fibres (eg, swollen mitochondria and nerve axons). Elevated BDNF release was significantly correlated with the abdominal pain scores. Meanwhile, abdominal withdrawal reflex scores to colorectal distension and mucosal protein gene product 9.5 immunoreactivity were significantly lowered in BDNF+/− than in BDNF+/+ mice. Electron microscopy showed degenerative changes on the mucosal nerve fibres in BDNF+/− mice. Exogenous BDNF induced an obvious dose-dependent increase in TrkB expression in dorsal root ganglia and dose-dependent decrease in threshold pressure in BDNF+/+ mice. Conclusions The increased expression of BDNF in colonic mucosa, together with the structural alterations of mucosal innervation, may contribute to the visceral hyperalgesia in IBS.