肾纤维化是慢性肾脏病发展到终末期肾衰竭的共同通路，上皮-间质转分化(EMT)是肾纤维化发生的中心环节之一，EMT的关键转录因子Snail1是Wnt通路的下游靶基因。课题组研究发现，生地水提物能减少UUO大鼠肾脏胶原沉积，缓解肾纤维化，并下调Wnt5a、β-catenin、α-SMA表达，上调E-cadherin表达。推测生地水提物可能通过Wnt/β-catenin信号通路缓解肾纤维化。本项目以HK-2细胞和UUO模型为研究对象，探讨Wnt/β-catenin/snail1信号通路在生地水提物抑制EMT，缓解肾纤维化中的重要作用，分析生地水提物对Wnt/β-catenin/snail1信号通路关键蛋白的调控作用，阐明生地水提物抑制Wnt/β-catenin/snail1信号通路，阻抑EMT，缓解肾纤维化的机制。本项目为阐释中医药理论防治肾纤维化提供实验依据，对发掘防治肾纤维化药物有重要意义。

Renal fibrosis is the final common pathway of all kinds of chronic kidney disease progressing to end-stage renal failure. Epithelial-to-mesenchymal transition (EMT) is a crucial step in the pathogenesis of renal fibrosis. The key transcription factor responsible for EMT, Snail1, is one of target genes of Wnt/β-catenin signaling. Our previous studies showed that collagen deposition and interstitial fibrosis were decreased in unilateral ureteral occlusion (UUO) rats administrated by the aqueous extract of Radix Rehmanniae, which was accompanied with the decreasing expression of Wnt5a, β-catenin and α-SMA and increasing expression E-cadherin. Thus, it is supposed that the aqueous extract of Radix Rehmanniae may ameliorate renal fibrosis through inhibiting the Wnt/β-catenin/snail1 signal pathway, which may be associated with the prevention of EMT. For that reason, we plan to choose HK-2 cells and UUO rats as the objects of this study for discussing the important role of the Wnt/β-catenin/snail1 signal pathway in the EMT process of the renal fibrosis, and analysis the effect of the aqueous extract of Radix Rehmanniae on Wnt/β-catenin/snail1 signal pathway, which can help us to make clear if EMT inhibited by Wnt/β-catenin/snail1 signal pathway is the key mechanism on ameliorating renal fibrosis induced by the aqueous extract of Radix Rehmanniae. The purpose of this study is benefit to provide experimental evidence for explaining the theory of ameliorating renal fibrosis under Traditional Chinese Medicine mechanism and exploit new drug to control the development of renal fibrosis.