肠道神经-免疫系统与肠道健康密切相关。炎症性肠病（IBD）中肠道神经系统（ENS）损伤使神经因子分泌失调，加重免疫损伤。但肠道神经免疫调控的分子机制仍未完全阐明。海马钙结合蛋白1（HPCAL1）是重要的神经元钙感受器，在神经退行性疾病中表达异常，并致神经元损伤。中枢神经系统与ENS高度同源。申请人前期发现IBD动物模型损伤的ENS中HPCAL1上调，提示其可能是IBD中ENS损伤的关键分子，结合课题组新近发现该分子可通过ERK-P21抑制细胞增殖（Hepatology，2016），提出：HPCAL1-ERK-P21通路可能是IBD中ENS损伤及进一步免疫损伤的关键通路。本课题拟在体内外实验中，通过慢病毒系统调控该基因表达，应用免疫印迹、激光共聚焦等手段检测炎症因子、神经因子、ENS状态等以验证该假说。预期成果有助阐明该分子在IBD神经免疫调控中的重要价值，为IBD发病机制及治疗提供新视角。

Enteric nervous-immune system plays an important role in maintaining gut health. The damage of enteric nervous system(ENS) in inflammatory bowel disease(IBD) induces the disorder of neurotrophic factor secretion, enhances immune injury. But the molecular mechanisms of enteric nervous-immune system regulation in IBD are not yet fully understood. Hippocalcin-like protein 1(HPCAL1) is an important neuronal calcium sensor, abnormal expressed in neurodegenerative diseases, and causing neuronal injury. Central nervous system has high homology with ENS. In preliminary works, we found that HPCAL1 was increased in injured ENS in IBD, indicated that HPCAL1 may be a key molecule acting in ENS injury in IBD. And our research group recently illuminated that HPCAL1 inhibited cell proliferation by activating ERK-P21 pathway(this result has been published in Hepatology，2016). Based on these findings, we conjecture that activation of HPCAL1-ERK-P21 pathway would induce ENS injury and enhance immune injury. This hypothesis will be verified by further studies in vivo and vitro, we will regulate the expression of HPCAL1 by lentiviral system, and then detect the status of inflammatory cytokines. neurotrophic factors and ENS by immunoblotting, confocal laser scanning and other detection methods. Expected results will help clarify the role of HPCAL1 in enteric nervous-immune system regulation in IBD, and provide a new perspective for the pathogenesis and treatment of IBD.