供肾缺血再灌注损伤（IRI）是造成原发性移植肾功能延迟恢复（DGF）以及早期移植失败的主要原因。研究发现IRI程度与肾小管上皮细胞的自噬密切相关、自噬相关基因缺陷的小鼠肾脏IRI中损伤加重；自噬能够选择性下调TLR信号通路，且TLR4/NF-КB通路参与介导移植肾IRI。因此我们推测移植肾肾小管上皮细胞自噬水平的上调可能会减轻供肾IRI程度，其机制可能是自噬选择性下调TLR4/NF-КB通路。本课题拟在小鼠肾移植模型中应用Tat-Beclin 1诱导自噬，动物实验及体外实验中通过对自噬的监测和移植肾IRI程度的形态学及功能评价以明确其通过增加肾小管上皮细胞的自噬活动起保护作用，并进一步在人肾小管上皮细胞中以控制变量法调节TLR4表达，验证细胞自噬下调TLR4/NF-КB通路在移植肾IRI保护中存在关键调控作用。旨在阐明自噬在移植肾IRI发生及修复的分子机制，为DGF防治提供新的理论依据。

Ischemia-reperfusion injury (IRI) of graft kidney is the major cause for delayed graft function(DGF) and for early graft failure. Currently, studies have suggested that the extent of damage is closely related to the level of autophagy in renal tubular epithelial cells. Furthermore, the aggravated IRI was observed in autophagy-deficient mice. The analysis of the data from protein chip demonstrated that autophagy selectively down-regulates TLR signal pathway and TLR4/NF-КB pathway participated in the introduction of IRI. Therefore, we hypothesize that the increased activity of autophagy in renal tubular epithelial cells could protect the graft kidney from IRI. In order to clarify the accurate role of autophagy in transplanted kidney, we are going to apply Tat-Beclin 1, a strong autophagy-inducing agent, to mouse models with IRI, to detect the autophagic body via electron microscopy and to evaluate the level of IRI by using various parameters. And the increased autophagy further regulate the expression of TLR4 in human renal tubular epithelial cells by control variable method to verifying the key role of autophagy in graft IRI by down-regulating TLR4/NF-КB pathway. This project aims to clarify the molecular mechanism of autophagy in the process of ischemia-reperfusion injury in graft kidney and to provide the new theoretical basis to the prevention and therapy of DGF following kidney transplantation.