miR-200a调控p38α信号通路对肠外营养相关肝损害机制研究

肠外营养相关肝损害（PNALD）是肠外营养常见的并发症，其发病机制不明，临床防治困难。研究证实miR-200家族参与调控肝纤维化、肝肿瘤侵袭等多种肝病发病过程，但迄今尚未报道miR-200家族与PNALD的关系。我们预实验结果提示miR-200a表达改变和p38α信号通路活化在PNALD中起重要作用。靶点预测显示p38α为miR-200a的下游靶基因，那么miR-200a很可能通过调控p38α信号途径影响PNALD发生。为此，我们将通过人肝细胞株和大鼠肠外营养肝损害模型，利用双荧光素酶报告系统、Western blot 及RNA干扰等技术，从分子、细胞、组织和动物整体水平等多方面探讨miR-200a及p38α信号通路活化在PNALD中的具体功能；明确miR-200a调控p38α信号通路的分子机制。本研究将从miR-200a这个新视点为完善PNALD发生机制奠定基础，为临床防治提供新思路。

Parenteral nutrition-associated liver disease (PNALD) is one of common complications that are induced by parenteral nutrition (PN). Currently, prevention and treatment of PNALD is still very difficult because of the unclear pathogenesis. The previous studies demonstrated that miR-200s were involved in a variety of liver diseases, including liver fibrosis and liver tumor invasion, but the relationship between miR-200s and PNALD has not yet been reported. Our previous studies suggested that changes of miR-200a expression and activation of p38α signaling played an important role the in the PNALD. miRNA target prediction tools analysis showed that p38α was a downstream target of miR-200a. Thus, we proposed a hypothesis that the miR-200a probably participated in the PNALD by regulating p38α signaling pathway. To test this hypothesis, we will explore the roles of miR-200a and p38α signaling in PNALD on the molecular, cellular, tissues and even animals levels with using experiments including dual-luciferase reporter system, Western blot and RNA interference on the base of human liver cell line and rat model of PNALD. Furthermore, the molecular mechanisms for miR-200a regulating p38α signaling pathway will be defined in this study. In a word, this study will be helpful in revealing the mechanism of PNALD and providing new ideas for the prevention and treatment of PNALD from a new perspective miR-200a.