金汁通过NF-κB信号通路介导肠上皮细胞自噬修复脓毒症肠黏膜屏障损伤机制的研究

肠黏膜屏障（IMB）损伤内毒素移位是脓毒症发生的重要机制之一。金汁治疗脓毒症等温热病历史悠久且疗效确切。金汁是将健康人粪便泉水淘洗，竹筛过滤，瓦罐密封埋入地下形成的中药。我们前期研究发现金汁可修复脓毒症损伤的IMB和改善肠道微生态，但作用机制不明。金汁促进肠上皮细胞自噬及减少肠黏膜中TNF-α、IL-6、Caspase-8的表达。这些因子都是NF-κB信号通路中关键作用因子，激活本通路介导肠上皮细胞自噬。据此提出假设：金汁可能通过NF-κB信号通路介导肠上皮细胞自噬修复脓毒症肠黏膜屏障。为此，拟探讨：（1）细胞共培养证实金汁通过NF-κB通路调节上皮细胞自噬及通透性；（2）体内小鼠脓毒症模型确证金汁介导NF-κB通路调控上皮细胞自噬及修复肠黏膜屏障，并对菌膜的影响；（3）探讨金汁经过NF-κB通路介导上皮细胞自噬及修复肠黏膜屏障的分子机制。本研究为金汁治疗脓毒症等急危重症提供理论依据。

The intestinal mucosal barrier（IMB）injury and endotoxin translocation into the circulatory syste are the major cause of sepsis.Jinzhi is a kind of traditional Chinese medicine which is formed by washing the fecal of healthy people with spring water, filtering with bamboo screen or gauze, sealing the pot and burying it underground. Jinzhi is one of the most effective treatments of sepsis and has a very long history. Jinzhi can protect IMB and improve the environment of microbial flora in intestinal canal, but the mechanism of Jinzhi to protect IMB can not be expound. In our previous studies on mouse, we have found that Jinzhi can increase the autophagy of enterocyte, TNF-α、IL-6 and Caspase-8 in the small intestinal tissue. While TNF-α、IL-6 and Caspase-8 are key factors of the NF-κB signal pathways and activating this pathway can increase the autophagy of enterocyte. In the present study, through analyzing the regulation of NF-κB signal pathway to the autophagy of enterocyte. Therefore the hypothesis that Jinzhi possibly repairs IMB through autophagy of intestinal epithelial cells mediating the NF-κB signaling pathway is proposed. In this study the model that Jinzhi intervene mouse of sepsis and Jinzhi containing serum intervene enterocyte are adopted. Research contents:1.The healing effect of the Jinzhi influence intestinal mucosal barrier through mediating the NF-κB signaling pathway by co-culture of enterocyte;2. Jinzhi regulate the autophagy of enterocyte and tight junction of enterocyte through mediating the NF-κB signaling pathway by mouse of sepsis. 3.The mechanism of the Jinzhi regulate autophagy of enterocyte through mediating the NF-κB signaling pathway.The purpose of the study is to testify the hypothesis that Jinzhi possibly repairs IMB through autophagy of intestinal epithelial cells mediating the NF-κB signaling pathway. The study lay the foundation for promotion of the Chinese medicine to treat sepsis and critically ill.