慢性肾脏病（CKD）持续的系统性炎症状态及氧化应激反应与疾病预后密切相关。诸多证据表明肠道菌群移位，肠屏障损伤及肠道氧化应激反应是导致系统性炎症的主要机制之一，肠道有望成为防治CKD新的干预靶点。本项目从尿毒素诱导的肠道氧化应激炎症反应这一视角，以肠道Keap1-Nrf2体系失衡为切入点，结合CKD脾肾亏虚，湿浊瘀血内蕴的关键病机，以扶肾颗粒为研究载体，围绕“扶肾颗粒通过调控尿毒素介导的Nrf2/ROS/NF-κB信号转导，减轻肠道氧化应激炎症反应及肠上皮屏障损伤，改善慢性肾脏病内环境下的肠道菌群移位，进而减轻肠源性的全身系统性炎症反应”这一假说，以肠道氧化应激炎症激活的Nrf2/NF-κB信号转导为研究主体，在体和离体实验相结合，从多层面结合生化，病理、免疫组化及分子生物学等技术，动态观察尿毒素诱导的信号激活及肠道损伤效应，探讨扶肾颗粒干预尿毒素诱导的肠源性氧化应激炎症反应的深层机制。

Systemic inflammation and oxidative stress are two major components involved in the pathogenesis and progression of chronic kidney disease. Evidences showed that altered gut microbiome, impaired mucosal barrier, and gut-induced oxidative stress were the main causes contributing to systemic inflammation. Gut is supposed to be a promising new target of intervention. Combining the pathogenesis of deficiency of spleen and kidney with stasis of dampness and blood, the study focuses on the imbalance of Keap1-Nrf2 system and puts forwards the hypothesis of Fushenkeli to regulate uremia-induced Nrf2/ROS/NF-κB cellular signal transduction and to alleviate gut oxidative stress, inflammation, intestinal epithelial barrier disruption and gut induced systemic inflammation. With a combination of pathologic morphology, immunohistochemistry and molecular biology technology, the study explores the underlying mechanism of Fushenkeli on uremic toxin-induced gut oxidative stress and inflammation in vivo and in vitro, via dynamic observation on the cellular transduction of Nrf2/NF-κB and the impaired mucosal barrier.