Brain-derived neurotrophic factor accelerates gut motility in slow-transit constipation
Brain-derived neurotrophic factor accelerates gut motility in slow-transit constipation
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脑源性神经营养因子加速慢传输型便秘的肠道蠕动
DOI：
10.1111/apha.12374
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发表时间：
2014-11-01
影响因子：
6.3
通讯作者：
Li, Y.
中科院分区：
文献类型：
--
作者：
Chen, F.;Yu, Y.;Li, Y.
背景与目的脑源性神经营养因子（BDNF）可能在肠道运动中发挥关键作用。我们的目的是探讨BDNF对慢传输型便秘(STC)肠道蠕动的生理影响，并探讨其潜在的分子机制。方法首先研究STC患者BDNF的表达和结肠神经纤维密度的变化。然后在体内和体外检查 BDNF 对 BDNF+/- 小鼠和洛哌丁胺诱导的便秘小鼠胃肠动力的影响。研究了平滑肌肌动蛋白（-SMA）表达以及神经纤维、神经肌肉接头（NMJ）和平滑肌细胞（SMC）的改变。最后，研究BDNF诱导的TrkB-磷脂酶C/肌醇三磷酸（TrkB-PLC/IP3）通路激活对肠道运动的影响。结果在STC患者中，BDNF表达和神经纤维密度降低，并且粘膜神经纤维超微结构变性。 BDNF+/- 和便秘小鼠的肠道蠕动在体内和体外均下降，BDNF 剂量依赖性地增加肠道蠕动。在BDNF+/-小鼠中，-SMA表达和神经纤维密度降低，并观察到神经纤维、NMJ和SMC超微结构变性。最后，TrkB-PLC/IP3通路拮抗剂显着减弱BDNF对肠道运动的兴奋作用，外源性BDNF诱导IP3表达明显增加。结论BDNF在STC中肠道运动中发挥重要的调节作用。它是通过改变肠道神经支配结构以及通过涉及 TrkB-PLC/IP3 途径激活的机制引起平滑肌继发性变性来介导的。
Background&AimsBrain-derived neurotrophic factor (BDNF) may play a critical role in gut motility. We aimed to investigate BDNF's physiologic effects on gut motility in slow-transit constipation (STC) and to explore the underlying molecular mechanisms.MethodsBDNF expression and alterations of colonic nerve fibre density in STC patients were first investigated. BDNF's effects on gastrointestinal motility of both BDNF+/- mice and loperamide-induced constipation mice were then examined in vivo and in vitro. Smooth muscle -actin (-SMA) expression, and nerve fibre, neuromuscular junction (NMJ) and smooth muscle cell (SMC) alterations were investigated. Finally, the effects of BDNF-induced TrkB-phospholipase C/inositol trisphosphate (TrkB-PLC/IP3) pathway activation on gut motility were investigated.ResultsIn STC patients, BDNF expression and nerve fibre density were decreased, and mucosal nerve fibre ultrastructural degenerations were demonstrated. Gut motility was decreased in vivo and in vitro in BDNF+/- and constipation mice, with BDNF dose-dependently increasing gut motility. In BDNF+/- mice, -SMA expression and nerve fibre density were decreased, and nerve fibre, NMJ and SMC ultrastructural degenerations were observed. Finally, TrkB-PLC/IP3 pathway antagonists dramatically attenuated BDNF's excitatory effect on gut motility, and exogenous BDNF induced an obvious increase in IP3 expression.ConclusionsBDNF plays an important regulatory role in gut motility in STC. It was mediated by altering the intestinal innervation structure, as well as smooth muscle secondary degeneration through a mechanism involving TrkB-PLC/IP3 pathway activation.