早期断奶使仔猪肠上皮屏障受损，TGF-β1在肠上皮屏障损伤修复中发挥着重要作用，其作用机制不明。本研究以断奶仔猪和体外猪肠上皮屏障损伤模型，采用Ussing chamber、荧光定量PCR、western blotting、激光共聚焦显微镜、RNA干扰等技术，研究仔猪断奶后肠道TGF-β1及其受体、紧密连接的发育性变化以及与MAPKs和Smads信号通路的关系；研究TGF-β1对体外猪肠上皮屏障损伤模型的修复作用，并利用特异性通路阻断剂和RNA干扰技术，抑制或者沉默MAPKs或Smads信号通路，检测通路关键蛋白的活性变化以及对肠上皮屏障修复的影响，揭示两条通路之间的串话，解析TGF-β1发挥作用的关键靶点；研究TGF-β1及其诱生剂（氧化锌、植物活性成分）对仔猪肠上皮屏障损伤修复的影响，探讨TGF-β1介导的smads和MAPKs信号通路在肠上皮屏障损伤修复中的作用，为在分子水平开展肠屏障功能的营养调控研究提供靶点。项目研究可为防治仔猪早期断奶综合症开辟一条新思路，具有重要理论意义和应用价值。

Early weaning has been shown to impair the intestinal epithelial barrier of piglets. Transforming growth factor beta 1 (TGF-β1) plays an important regulatory role in the restoration of intestinal epithelial barrier. However, the mechanisms have not yet been elucidated. Using the experimental technique, such as Ussing chamber, confocal laser scanning microscopy, functional classific gene chip, co-immunoprecipitation, the distribution and developmental changes of TGF-β1 and its receptors in the intestine in association with tight junction and Smads and mitogen-activated protein kinase (MAPKs) signaling pathways are studied in the weaned pig. The effects of TGF-β1 on the restoration of damaged intestinal epithelial barrier are determined in vitro cultured IPEC-J2. MAPKs or Smads are knockdowned by lentivirus-mediated RNA interference in cultured IPEC-J2 cell. Then the effects on tight junctions and their protein, TGF-β1 and its receptors, Smads and ERK signaling pathways are studied. Cross-talk between MAPKs and Smad signaling pathways is investigated. Our aims are to delineate the mechanisms behind TGF-β1-induced barrier enhancement and to determine how TGF-β1 could restitute tight junction disruption. The elucidation of TGF-β1-mediated Smads and MAPKs signaling pathways on the restoration of intestinal epithelial barrier will not only create some theory, but also provide a new target to the nutrition regulation of intestinal barrier function.