脱氧雪腐镰刀菌烯醇(DON)是污染谷物和饲料最严重的霉菌毒素之一，可导致动物拒食。肠道内分泌细胞表面的钙敏感受体(CaSR)可识别毒物，经CaSR-TRPM5信号通路诱导饱感激素分泌，负反馈调节食欲中枢，导致拒食。我们研究发现，DON能诱导饱感激素CCK和PYY分泌，与拒食呈正相关；阻断CaSR下调DON诱导的饱感激素分泌和拒食。在此基础上，我们提出“DON诱导拒食的上游机制是DON激活CaSR，诱导饱感激素分泌；下游机制是饱感激素负反馈调节食欲中枢，诱导拒食”。为证实这一假说，本课题以药理阻断和基因沉默或敲除为平行观察手段，在前期STC-1细胞的研究基础上，从原代肠道内分泌细胞层面阐释DON诱导饱感激素分泌的CaSR-TRPM5信号通路；揭示CaSR对DON诱导的饱感信号传导和拒食神经元激活的调控作用。从饱感激素负反馈调节的视角，揭示DON诱导拒食的机制，为有效防治DON中毒提供新思路。

Deoxynivalenol (DON) is one of the most serious mycotoxin which severely contaminates grains and feeds in the world. Exposure to DON causes anorexia in animal. Calcium-sensing receptor (CaSR) is believed to function as a toxin sensor on enteroendocrine cell and a mediator of satiety hormone release through CaSR-TRPM5 signaling pathway. Satiety hormone will activate anorexigenic neurons via negative-feedback regulation of appetite center and eventually cause anorexia. Our preliminary experiments indicated that exposure to DON induced satiety hormones cholecystokinin (CCK) and peptide YY (PYY) release, which were correlative to DON-induced anorexia. While, blocking CaSR could down-regulate DON-induced satiety hormone release and anorexia. Based on our findings, our lab proposed a hypothesis, "Upstream mechanism of DON-induced anorexia is that DON will activate CaSR and induce satiety hormone release; Downstream mechanism of DON-induced anorexia is that negative-feedback regulation of appetite center by satiety hormone induces anorexia". In order to verify this hypothesis, our lab will elucidate mechanisms of DON-induced anorexia by using respective receptor blocking and gene silencing or gene knockout as parallel techniques. We will investigate CaSR-TRPM5 signaling pathway for DON-induced satiety hormones CCK and PYY release using primary murine enteroendocrine cell, based on our findings in STC-1 cell. Then we will explore whether CaSR plays a role in regulating satiety signal transduction and activation of anorexigenic neurons. The ultimate goal of these studies is to further reveal mechanisms of DON-induced anorexia from negative-feedback regulation perspective. These findings are expected to offer significant ideas that will discover efficacious interventions to food poisoning of DON over what we have known up to date.