NR2B通过mBDNF参与肠易激综合征内脏高敏感的发生

NR2B contributes to visceral hypersensitivity in irritable bowel syndrome via mBDNF

目的在神经系统,NMDA受体(NMDARs)NR2B亚基参与内脏高敏感的发生,本研究探讨在肠黏膜,该NR2亚型是否通过m BDNF(m BDNF)参与肠易激综合征内脏高敏感的发生。方法共纳入32例参与者,检测肠黏膜NR2B及m BDNF的表达水平。用Pearson线性相关分析NR2B与m BDNF表达水平的关系;用Spearman秩相关分析m BDNF表达水平与腹部疼痛评分的关系;以NMDA受体激动剂、NMDA受体阻滞剂、NR2B特异性阻滞剂干预细胞,ELISA法检测培养基中m BDNF蛋白表达水平的变化。结果腹泻型肠易激综合征(IBS-D)组肠黏膜组织NR2B及m BDNF蛋白表达水平均明显高于对照组(NR2B:90.22±30.79 vs 63.47±28.19,P=0.016;m BDNF:89.91±20.95 vs 56.53±22.25,P<0.001),且两者表达水平呈正相关。m BDNF表达水平与腹部疼痛评分呈正相关。NMDA受体活化后可诱导m BDNF表达增加,该作用可完全被NMDA受体阻滞剂、NR2B特异性阻滞剂抑制。结论 NR2B亚基通过诱导m BDNF的表达参与IBS-D患者内脏高敏感的发生。

Objective In the nervous system, N-methyl-D-aspartate receptors （NMDARs） subunit NMDA receptor 2B （NR2B） is involved in visceral hypersensitivity. This study aims to investigate if colonic mucosal NR2B contributes to visceral hypersensitivity in irritable bowel syndrome via mature brain-derived neurotrophic factor （mBDNF）. Methods A total of 32 participants were included. Colonic mucosal NR2B subunits and mBDNF expressions were detected. The relationship between the NR2B and mBDNF expressions was analyzed with Pearson correlation analysis. The rela- tionship between mBDNF expression and abdominal pain scores was analyzed with Spearman correlation analysis. After administration of NMDARs agonist, NMDARs antagonist and NR2B subunit antagonist, the expression of mBDNF in cell culture supernatant was assessed with ELISA. Results NR2B and mBDNF expressions were significantly increased in colonic mucosa of IBS-D patients （NR2B： 90.22 ±30.79 vs 63.47 ±28. 19, P =0. 016; mBDNF： 89.91 ±20.95 vs 56.53 ± 22. 25, P 〈 0. 001 ）. NR2B expression was positively correlated with mBDNF expression. Furthermore, mBDNF expression was positively correlated with abdominal pain scores. The activation of NMDAR induced mBDNF expression, which could be completely inhibited by NMDARs antagonist and NR2B subunit antagonist. Conclusion NR2B contributes to visceral hypersensitivity in IBS-D via mBDNF.