EGF/EGFR-MAPKs-MicroRNAs在猪小肠黏膜热损伤后的修复机制

The small intestine plays critical role in nutrient absorption and mucosal immune, however extreme heat stress-induced injury in small intestine is becoming more common, especially during the summer. The intestinal epithelium has rapid turnover rates as mature differentiated epithelial cells are shed into the lumen and are continuously replaced by the progeny of stem cells, so the damaged epithelial cells are continually and rapidly replaced by new cells, crucial for maintaining sufficient intestinal function. In the current study we employed both in vivo (pig) and in vitro (small intestinal epithelial cells, IPEC / IEC) heat stress model to investigate the molecular mechanisms of EGF / EGFR- MAPKs AP-1/NF-κB-MicroRNA pathway in the injury repair/regeneration process.We also intend to evaluat the regulation of volatile oil in the repair process.

肠道是营养物质消化吸收的主要场所，是机体最大的黏膜免疫屏障。高温应激时，小肠绒毛严重缺氧、缺血损伤，因此胃肠道是动物应激的中心器官之一。本研究采用体内（猪）和体外（小肠上皮细胞，IPEC/IEC）热应激模型，观察小肠黏膜组织病理损伤和肠上皮细胞的超微结构变化，结合基因芯片差异显示技术研究体内外EGF/EGFR-MAPKs信号通路、核转录因子AP-1/NF-κB-MicroRNA在猪小肠黏膜热损伤过程中的修复机制，评价苍术和藿香挥发油在调控小肠隐窝干细胞增殖、分化、移行中的修复机制，通过整合体内外试验结果探讨EGF/EGFR-MAPKs信号通路及AP-1/NF-κB-MicroRNA在热损伤中修复调控的网络关系，从正反两个方面锁定损伤的小肠黏膜修复相关的药物作用靶点，为今后的研究奠定基础。

肠道是营养物质消化吸收的主要场所，是机体最大的黏膜免疫屏障。高温应激时，小肠绒毛严重缺氧、缺血损伤，因此胃肠道是动物应激的中心器官之一。本研究采用体内（猪）和体外（小肠上皮细胞，IPEC/IEC）热应激模型，观察小肠黏膜组织病理损伤和肠上皮细胞的超微结构变化，结合基因芯片差异显示技术研究体内外EGF/EGFR-MAPKs信号通路、核转录因子AP-1/NF-κB-MicroRNA在猪小肠黏膜热损伤过程中的修复机制，评价苍术和藿香挥发油在调控小肠隐窝干细胞增殖、分化、移行中的修复机制，通过整合体内外试验结果探讨EGF/EGFR-MAPKs信号通路及AP-1/NF-κB-MicroRNA在热损伤中修复调控的网络关系。结果显示苍术和藿香挥发油可通过上调EGF和EGFR的基因表达，抑制AP-1/NF-κB-MicroRNA激活，而促进细胞增殖，提高细胞活力。从正反两个方面锁定损伤的小肠黏膜修复相关的药物作用靶点，为今后的研究奠定基础。