Graduate School, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.
World J Gastroenterol. 2019 Jan 14;25(2):269-281. doi: 10.3748/wjg.v25.i2.269.
BACKGROUND: Visceral hypersensitivity is considered to play a vital role in the pathogenesis of irritable bowel syndrome (IBS). Neurotrophins have drawn much attention in IBS recently. Brain-derived neurotrophic factor (BDNF) was found to mediate visceral hypersensitivity facilitating sensory nerve growth in pre-clinical studies. We hypothesized that BDNF might play a role in the pathogenesis of diarrhea-predominant IBS (IBS-D). AIM: To investigate BDNF levels in IBS-D patients and its role in IBS-D pathophysiology. METHODS: Thirty-one IBS-D patients meeting the Rome IV diagnostic criteria and 20 age- and sex-matched healthy controls were recruited. Clinical and psychological assessments were first conducted using standardized questionnaires. Visceral sensitivity to rectal distension was tested using a high-resolution manometry system. Colonoscopic examination was performed and four mucosal pinch biopsies were taken from the rectosigmoid junction. Mucosal BDNF expression and nerve fiber density were analyzed using immunohistochemistry. Mucosal BDNF mRNA levels were quantified by quantitative real-time polymerase chain reaction. Correlations between these parameters were examined. RESULTS: The patients had a higher anxiety score [median (interquartile range), 6.0 (2.0-10.0) 3.0 (1.0-4.0), = 0.003] and visceral sensitivity index score [54.0 (44.0-61.0) 21.0 (17.3-30.0), < 0.001] than controls. The defecating sensation threshold [60.0 (44.0-80.0) 80.0 (61.0-100.0), = 0.009], maximum tolerable threshold [103.0 (90.0-128.0) 182.0 (142.5-209.3), < 0.001] and rectoanal inhibitory reflex threshold [30.0 (20.0-30.0) 30.0 (30.0-47.5), = 0.032] were significantly lower in IBS-D patients. Intestinal mucosal BDNF protein [3.46E-2 (3.06E-2-4.44E-2) 3.07E-2 (2.91E-2-3.48E-2), = 0.031] and mRNA [1.57 (1.31-2.61) 1.09 (0.74-1.42), = 0.001] expression and nerve fiber density [4.12E-2 (3.07E-2-7.46E-2) 1.98E-2 (1.21E-2-4.25E-2), = 0.002] were significantly elevated in the patients. Increased BDNF expression was positively correlated with abdominal pain and disease severity and negatively correlated with visceral sensitivity parameters. CONCLUSION: Elevated mucosal BDNF may participate in the pathogenesis of IBS-D facilitating mucosal nerve growth and increasing visceral sensitivity.
背景：内脏敏感性被认为在肠易激综合征（IBS）的发病机制中起着至关重要的作用。神经生长因子最近在 IBS 中引起了广泛关注。研究发现脑源性神经营养因子（BDNF）可介导内脏敏感性，促进感觉神经生长。我们假设 BDNF 可能在腹泻型肠易激综合征（IBS-D）的发病机制中发挥作用。
目的：研究 IBS-D 患者的 BDNF 水平及其在 IBS-D 病理生理学中的作用。
方法：招募了 31 名符合罗马 IV 诊断标准的 IBS-D 患者和 20 名年龄和性别匹配的健康对照者。首先使用标准化问卷进行临床和心理评估。使用高分辨率测压系统测试直肠扩张的内脏敏感性。进行结肠镜检查，并从直肠乙状结肠交界处采集 4 个黏膜夹活检。使用免疫组织化学分析黏膜 BDNF 表达和神经纤维密度。通过实时定量聚合酶链反应定量黏膜 BDNF mRNA 水平。检查这些参数之间的相关性。
结果：与对照组相比，患者的焦虑评分[中位数（四分位距），6.0（2.0-10.0） 3.0（1.0-4.0）， = 0.003]和内脏敏感性指数评分[54.0（44.0-61.0） 21.0（17.3-30.0）， < 0.001]更高。排便感觉阈值[60.0（44.0-80.0） 80.0（61.0-100.0）， = 0.009]、最大耐受阈值[103.0（90.0-128.0） 182.0（142.5-209.3）， < 0.001]和直肠肛门抑制反射阈值[30.0（20.0-30.0） 30.0（30.0-47.5）， = 0.032]明显更低。肠黏膜 BDNF 蛋白[3.46E-2（3.06E-2-4.44E-2） 3.07E-2（2.91E-2-3.48E-2）， = 0.031]和 mRNA[1.57（1.31-2.61） 1.09（0.74-1.42）， = 0.001]表达和神经纤维密度[4.12E-2（3.07E-2-7.46E-2） 1.98E-2（1.21E-2-4.25E-2）， = 0.002]在患者中明显升高。BDNF 表达增加与腹痛和疾病严重程度呈正相关，与内脏敏感性参数呈负相关。
结论：升高的黏膜 BDNF 可能参与 IBS-D 的发病机制，促进黏膜神经生长并增加内脏敏感性。
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