Nrf2和NFκB信号通路在糖尿病膀胱发生发展中的作用及机制研究

DCP的发病与外周神经功能障碍、膀胱逼尿肌功能失调和尿路上皮改变密切相关，且疾病的不同时期膀胱感觉功能和逼尿肌运动功能也发生相应改变。Nrf2通路的激活可以保护神经功能，防止肌肉损伤；NF-κB通路的抑制可以降低神经炎症损伤、改善感觉功能、减少细胞凋亡。我们前期实验结果也证实，Nrf2基因敲除小鼠排尿功能发生改变；葡萄多酚可以激活Nrf2通路，改善8周糖尿病大鼠膀胱功能。目前Nrf2通路在DCP中的作用国内外尚未有文献报道。因此，我们提出Nrf2和NF-κB通路在DCP的发生发展中发挥重要作用这一假设。本项目拟以Nrf2和NF-κB通路的改变为切入点，从膀胱感觉功能和运动功能两个角度，深入探究在DCP的不同阶段， Nrf2和NF-κB通路的改变对膀胱感觉功能和运动功能的作用，以及膀胱氧化应激状态、细胞凋亡水平、神经生长因子等变化情况。从而为DCP防治提供理论基础及潜在的作用靶点。

The development and progression of diabetic cystopathy are closely related with the neurological dysfunction, the detrusor dysfunction and the changes of urothelium. The sensory and motor function of the bladder are impaired in different stages of DCP. Activation of Nrf2 pathway can protect neural function and prevent muscle damage while inhibition of NF-κB signaling pathway could alleviate nerve inflammation injury, improve sensory function and decrease Level of apoptosis. We also found that the urinary function was changed in Nrf2-/- mice and grape polyphenols activating the Nrf2 pathway could improve diabetic bladder function in the preliminary research. Currently the role of Nrf2 pathway in the DCP have not been reported. Therefore, we proposed that Nrf2 and NF-κB pathway plays an important role in the development of diabetic neurogenic bladder. the project intends to study the effect of changes of Nrf2 and NF-κB pathway on the bladder sensory and motor functions. Furthermore, the changes of oxidative stress , apoptosis levels and the expression of nerve growth factor in bladder will be explored in our project. The aim of our project is providing a theoretical basis and possible new therapeutic targets for DCP.