Poli E, Lazzaretti M, Grandi D, Pozzoli C, Coruzzi G
Institute of Pharmacology, University of Parma, Italy.
Neurochem Res. 2001 Sep;26(8-9):1085-93. doi: 10.1023/a:1012313424144.
The 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced model of experimental colitis was used to investigate the time-course of alterations in enteric neurotransmission and/or smooth muscle function that occur in chronic inflammation. Myenteric plexus morphology (immunocytochemical markers), functional integrity of cholinergic neurons (3H-choline uptake, acetylcholine release and contractile response to electrical field stimulation) and smooth muscle integrity (contractile response to exogenous acetylcholine) were determined 2, 7, 15, and 30 days after TNBS treatment. In TNBS-treated rats extensive ulcerations of the mucosa and/or the submucosa and increase in colonic weights were accompanied by significant reduction in 3H-choline uptake, acetylcholine release and contractile response to stimulation of enteric nerves. These changes were maximal 7 and 15 days after TNBS treatment. Immunocytochemical marker (PGP 9.5, SNAP 25, synaptophysin and S100 protein) expression was absent in necrotic areas of colons removed 7 days post-injury and partially reduced in colons removed 15 days after TNBS treatment. By contrast, the contractile response to exogenous acetylcholine was significantly increased after 7 days in both inflamed and uninflamed regions and returned to control values by day 30. Likewise, an almost complete recovery of neural cholinergic function and of myenteric plexus morphology was observed 30 days after TNBS treatment. These data suggest that TNBS-induced colitis is associated with progressive and selective alterations in myenteric plexus structure and function, with consequent reduction of cholinergic neurotransmission and abnormality in colonic contractility. The reversibility of myenteric plexus disruption is a clear indication of neuronal plasticity within enteric nervous system as an adaptative mechanism against inflammatory challenges.
采用2,4,6-三硝基苯磺酸（TNBS）诱导的实验性结肠炎模型，来研究慢性炎症过程中发生的肠神经传递和/或平滑肌功能改变的时间进程。在TNBS处理后2、7、15和30天，测定肌间神经丛形态（免疫细胞化学标志物）、胆碱能神经元的功能完整性（3H-胆碱摄取、乙酰胆碱释放以及对电场刺激的收缩反应）和平滑肌完整性（对外源性乙酰胆碱的收缩反应）。在TNBS处理的大鼠中，黏膜和/或黏膜下层广泛溃疡以及结肠重量增加，同时伴有3H-胆碱摄取、乙酰胆碱释放以及对肠神经刺激的收缩反应显著降低。这些变化在TNBS处理后7天和15天最为明显。损伤后7天切除的结肠坏死区域中，免疫细胞化学标志物（PGP 9.5、SNAP 25、突触素和S100蛋白）表达缺失，而在TNBS处理后15天切除的结肠中部分降低。相比之下，在炎症和非炎症区域，对外源性乙酰胆碱的收缩反应在7天后均显著增加，并在第30天恢复到对照值。同样，在TNBS处理30天后，观察到神经胆碱能功能和肌间神经丛形态几乎完全恢复。这些数据表明，TNBS诱导的结肠炎与肌间神经丛结构和功能的进行性和选择性改变相关，从而导致胆碱能神经传递减少和结肠收缩异常。肌间神经丛破坏的可逆性清楚地表明，肠神经系统内的神经元可塑性是一种对抗炎症挑战的适应性机制。
