Abstract：
Enteric neuropathy underlies long-term gastrointestinal (GI) dysfunction associated with several pathological conditions. Our previous studies have demonstrated that structural and functional changes in the enteric nervous system (ENS) result in persistent alterations of intestinal functions long after the acute insult. These changes lead to aberrant immune response and chronic dysregulation of the epithelial barrier. Damage to the ENS is prognostic of disease progression and plays an important role in the recurrence of clinical manifestations. This suggests that the ENS is a viable therapeutic target to alleviate chronic intestinal dysfunction. Our recent studies in preclinical animal models have progressed into the development of novel therapeutic strategies for the treatment of enteric neuropathy in various chronic GI disorders. We have tested the anti-inflammatory and neuroprotective efficacy of novel compounds targeting specific molecular pathways. Ex vivo studies in human tissues freshly collected after resection surgeries provide an understanding of the molecular mechanisms involved in enteric neuropathy. In vivo treatments in animal models provide data on the efficacy and the mechanisms of actions of the novel compounds and their combinations with clinically used therapies. These novel findings provide avenues for the development of safe, cost-effective, and highly efficacious treatments of GI disorders.
摘要：
肠神经病是与几种病理状况相关的长期胃肠道（GI）功能障碍的基础。我们先前的研究表明，肠神经系统（ENS）的结构和功能变化会在急性损伤后很长一段时间内导致肠功能的持续改变。这些变化导致异常的免疫应答和上皮屏障的慢性失调。对ENS的损害是疾病进展的预后，在临床表现的复发中起重要作用。这表明ENS是缓解慢性肠功能障碍的可行治疗靶标。我们最近在临床前动物模型中的研究已经进展到用于治疗各种慢性胃肠道疾病中的肠神经病的新型治疗策略的开发。我们已经测试了靶向特定分子途径的新型化合物的抗炎和神经保护功效。在切除手术后新鲜收集的人体组织中的离体研究提供了对涉及肠神经病变的分子机制的理解。动物模型中的体内治疗提供了关于新型化合物及其与临床使用的疗法的组合的功效和作用机制的数据。这些新颖的发现为安全的发展提供了途径，成本效益高,和胃肠道疾病的高效治疗。
