呕吐毒素导致仔猪肠道防御肽表达紊乱的分子机制及其营养调控

Deoxynivalenol (DON) is one of the most pervasive mycotoxin, which is commonly found in animal feeds and feed ingredients. Our previous study in porcine intestinal epithelial cell line IPEC-J2 demonstrated that DON could inhibit the expression of host defense peptides. As the efficient defense components of the innate immunity, host defense peptides dysregulation would result in decreased disease resistance, posing a health hazard to pigs. To explore the mechanism of DON in disturbing the expression of intestinal host defense peptides in piglets and the development of nutritional strategies to prevent its adverse effects are of great theoretical significance and urgent practical value in promoting the healthy progress of swine industry. This study aims to determine the interference effects of DON on the intestinal porcine host defense peptides expression in piglets and IPEC-J2 cells. Furthermore, RNAi technology or specific inhibitors will be used to identify the role of NOD2 and caspase-12 in DON induced dysregulation of host defense peptides using IPEC-J2 cells. On this basis, we will then investigate whether the nutrient (butyrate) could alleviate DON induced intestinal injury through modulation of the host defense peptides expression via NOD2/caspase-12 pathway. This study has theoretical significance and practical value to guide pig production and feed preparation.

呕吐毒素（DON）是我国饲料与原料中污染严重的霉菌毒素。我们前期研究发现DON能抑制猪肠上皮细胞防御肽的表达。宿主防御肽作为天然免疫系统的重要组成部分，其表达紊乱会导致动物抗病力下降，对养猪业危害极大。探明DON干扰仔猪肠道防御肽表达的机制及其营养干预的可行性，对预防DON的危害，促进养猪业健康发展具有重要的理论意义和迫切的实际价值。本项目以NOD2/caspase-12通路调控防御肽表达为出发点，构建断奶仔猪和猪肠上皮细胞DON应激模型，筛选DON致仔猪肠道中特异性表达紊乱的防御肽。应用RNA干扰或抑制剂手段鉴定NOD2和Caspase-12在DON干扰猪肠上皮细胞防御肽表达中的作用。在此基础上，探究营养素（丁酸）是否可以调控NOD2/caspase-12通路干预DON对猪肠道防御肽的表达，进而缓解DON致断奶仔猪肠道损伤的可行性。研究结果对指导养猪生产和饲料配制有理论意义和实际价值。

呕吐毒素（DON）是我国饲料与原料中污染严重的霉菌毒素，对养猪生产危害极大。肠道是DON毒害的首要靶器官。宿主防御肽作为天然免疫系统的重要组成部分，其表达紊乱会导致动物抗病力下降，降低饲料报酬。本项目以NOD2/caspase-12通路调控宿主防御肽表达为出发点，构建了断奶仔猪和猪肠上皮细胞DON应激模型，筛选得到了DON致断奶仔猪肠道中特异性表达紊乱的防御肽，并鉴定了NOD2/caspase-12通路在DON干扰仔猪肠道防御肽表达中的作用。同时发现DON暴露能够抑制断奶仔猪肠道三叶肽的表达，SPDEF是DON抑制肠道三叶肽表达过程中的关键调节因子。此外，项目研究了DON暴露对断奶仔猪肠道微生物菌群的影响，筛选得到了介导DON致断奶仔猪厌食的关键微生物，建立了肠道微生物与DON致断奶仔猪厌食之间的潜在关系。在此研究基础上探索性发现，丁酸钠能够通过调节NOD2/caspase-12通路干预DON对仔猪肠道防御肽的表达，缓解了DON对断奶仔猪造成的生长抑制和肠道屏障功能损伤。项目的研究结果初步阐明了DON导致仔猪肠道防御肽表达紊乱的分子机制，揭示了丁酸缓解DON致断奶仔猪肠道损伤的可行性，对指导养猪生产和饲料配制具有重要的理论意义和实际价值。