基于氧化应激介导NF-κB信号活化研究清肾颗粒对肾小管上皮细胞转分化的影响

肾小管上皮细胞转分化（EMT）是肾间质纤维化发生的关键，研究其发病机制对延缓慢性肾衰进展有重要意义。湿热证与肾脏炎症状态及高表达炎症因子密切相关，具有清热化湿祛瘀功效的中药复方清肾颗粒可以通过抑制肾脏炎症反应发挥抗肾脏纤维化、改善肾功能作用，但其抗炎作用的信号转导机制尚不清楚。研究表明，NF-κB信号活化是启动炎症反应的重要因素，直接参与肾小管EMT、肾间质纤维化的发生发展；而氧化应激在肾小管EMT中起重要作用，能够诱导NF-κB信号活化。本研究以单侧输尿管梗阻（UUO）的肾间质纤维化大鼠和高糖诱导的人肾小管上皮细胞（HK-2）转分化的细胞模型为研究对象，从整体、细胞和基因蛋白表达层面深入研究氧化应激对NF-κB信号通路的调控机制及其该机制在肾小管EMT、肾间质纤维化中的作用；并进一步探讨清肾颗粒对氧化应激介导NF-κB信号活化的影响，揭示其发挥抗炎、抗肾脏纤维化的作用机制。

Renal tubular epithelial-mesenchymal transition（EMT）is the key step to renal interstitial fibrosis, so studying the mechanism could play an important role in postponing the CRF process. CRF damp-heat syndrome is closely related to inflammatory state of the kidney and high expression of inflammatory factors in a previous studies, while Clearing away Heat, Resolving Dampness and Removing Blood Stasis（CRR）and Qingshen Granule（a Traditional Chinese Medicine having the effect of CRR）Therapy can retard renal fibrosis and improve renal function through suppressing the inflammation of the kidney, but signaling pathway of anti-inflammatory effects is not clear.The data show that activated NF-κB is the key factor of initiating inflammation and it directly involve in the progress of renal tubular EMT and renal interstitial fibrosis. Oxidative stress play the important role in renal tubular EMT and it can induce the NF-κB activity. The rats model of unilateral ureter obstruction（UUO）and the cell model of renal tubular EMT induced by high glucose are established in this project to study the signaling mechanisms between oxidative stress and NF-κB, the effects on renal tubular EMT and renal interstitial fibrosis，and further observe the mechanism of oxidative stress activating NF-κB adjusted by Qingshen Granule. As a result, a new target for anti-inflammation and anti-fibrosis effect of Qingshen Granule can be revealed.