CRF营养不良发生率高，预后不良，发生机制不完全清楚，与骨骼肌蛋白质代谢密切相关，目前国内无知识产权的药物治疗。最新研究发现FXR-CREB轴调控的自噬信号广泛参与肿瘤骨骼肌蛋白质营养代谢，但在CRF营养不良所致PEW和骨骼肌萎缩的发生机制尚不清楚。本研究拟通过建立CRF营养不良大鼠模型，并采用siRNA/cDNA技术建立FXR-CREB轴沉默/过表达MSC和肌管模型，研究FXR-CREB轴与自噬信号（FXR、CREB、LC3-I/II、Atg7、Atg10、P62）对蛋白质代谢合成信号（Akt、mTOR）、分解信号（Atrogin-1、MuRF-1）、氨基酸运载体（LAT1、CAT-2A、CAT-2B）、MSC分化率以及分化标记物(Pax-7、MyoD)的影响，并用肾衰营养胶囊进行干预，探讨FXR-CREB轴在CRF营养不良发生中的作用及肾衰营养胶囊改善CRF营养不良的分子机制。

CRF malnutrition possesses high incidence and poor prognosis of CRF. Its mechanism remains unclear, and is closely related to protein metabolism in skeletal muscle. Until now no specific drugs were used in clinical treatment. Previous studies found that autophagy signaling are widely involved in protein metabolism in other cells, the FXR-CREB axis is a long-acting regulatory mechanism of autophagy signal, but the role in PEW caused by CRF malnutrition is still unclear. In order to investigate the role of FXR-CREB axis in CRF malnutrition, we plan to use CRF dystrophy animal model and FXR gene interference model for investigating the role of FXR-CREB axis related autophagy signaling (FXR, CREB, LC3-I/II, Atg7, Atg10, P62) on protein anabolism(Akt, mTOR), catabolism (Atrogin-1, MuRF-1), AA transporters (LAT1, CAT-2A, CAT-2B),MSC differentiation rate and differentiation markers(Pax-7, MyoD). Then we’d like to utilize capsule to investigate the drug effect of FXR-CREB axis in CRF malnutrition and protein metabolism. The theoretical basis of a proper treatment, which prevent CRF malnutrition, are warranted to be provided in our finding.