脑源性神经营养因子在结肠炎后内脏高敏感小鼠中的调节作用

摘要

脑源性神经营养因子(BDNF)可调控突触可塑性和维持神经内环境的稳定,近年研究证实BDNF参与痛觉的调控.目的:研究BDNF在结肠炎后内脏高敏感小鼠中的调节作用.方法:以结肠内灌注三硝基苯磺酸(TNBS)诱导建立结肠炎后内脏高敏感模型.将小鼠分为BDNW+/+对照组、BDNF+/+TNBS炎症组、BDNF+/-对照组和BDNF+/-TNBS炎症组.行结肠和膀胱组织学检查,以ELISA法测定背根神经节内BDNF蛋白表达,记录各组对结直肠扩张的反应和膀胱敏感性.结果:TNBS对两种基因型小鼠均可诱导明显的结肠炎症.同一基因型小鼠TNBS炎症组背根神经节BDNF表达显著高于相应对照组(P＜0.05),同时伴有结肠和膀胱敏感性上调(P＜0.05).BDNF+/- TNBS炎症组和对照组BDNF表达分别显著低于相应BDNF+/+小鼠(P＜0.05),BDNF+/- TNBS炎症小鼠的结肠和膀胱敏感性显著低于BDNF+/+TNBS炎症小鼠(P＜0.05).除结直肠扩张压力≥60 mm Hg外,BDNF+/-对照小鼠的结肠和膀胱敏感性与BDNF+/+对照小鼠无明显差异.结论:BDNF对结肠炎后结肠高敏感和牵涉性膀胱高敏感具有调节作用.%Brain-derived neurotrophic factor (BDNF) can modulate the plasticity of synapses and maintain the environment of nervous system. Recent studies show that BDNF is also involved in pain modulation. Aims: To investigate the role of BDNF in the modulation of post-inflammatory visceral hypersensitivity in mice. Methods: Colitis model was induced in mice by enema with 2,4,6-trinitrobenzene sulfonic acid (TNBS). BDNF+/+4 and BDNF+/- mice were divided into BDNF+/+ control group, BDNF+/+ TNBS-colitis group, BDNF+/- control group and BDNF+/- TNBS-colitis group. Histology examination of colon and bladder was performed. Expression of BDNF in dorsal root ganglia was determined by ELISA. Visceral response to colorectal distension and bladder sensitivity were recorded. Results: Colitis was successfully induced by TNBS in both genotypes mice. Expression of BDNF in dorsal root ganglia was significantly higher in both TNBS-colitis groups than that in corresponding control groups (P<0.05), and sensitivity of colon and bladder was up-regulated (P<0.05). Expression of BDNF in BDNF+/- TNBS-colitis group and BDNF+/- control group was significantly lower than that in BDNF+/+ TNBS-colitis group and BDNF+/+ control group, respectively (P<0.05). Sensitivity of colon and bladder in BDNF+/- TNBScolitis group was significantly lower than that in BDNF+/+ TNBS-colitis group (P<0.05), while no significant difference was found between BDNF+/- control group and BDNF+/+ control group except with colorectal distention≥60 mm Hg. Conclusions: BDNF participates in the modulation of post-inflammatory colonic and referred bladder hypersensitivity.