血管内皮细胞损伤在肾纤维化发生及进展中起重要作用，研究其发病机制对延缓CKD进展有重要意义。湿热证与肾脏炎症反应密切相关，具有清热化湿祛瘀功效的中药清肾颗粒通过降低CKD患者P-selectin水平，改善NO/ET失衡，达到保护血管内皮、改善肾功能作用，但对于P-selectin介导的相关信号通路及其调控机制尚不清楚。研究表明P-selectin与其配体PSGL-1结合后通过对MAPK信号通路调控机制介导了血管内皮炎性损伤和肾纤维化过程。本研究以5/6肾切除大鼠肾纤维化模型和LPS诱导人脐静脉内皮细胞（HUVEC）损伤模型为研究对象，探讨P-selectin/PSGL-1对MAPK家族中4条信号通路的调控机制及其在内皮细胞炎性损伤和内皮细胞-间充质转化（EndMT）中的作用，从内皮细胞损伤角度阐明肾纤维化机制；并观察清肾颗粒对上述信号通路转导和内皮损伤的干预作用，揭示其抗肾纤维化机理。

Vascular endothelial cell injury plays an important role in renal fibrosis, so studying the mechanism is important in postponing the process of Chronic Kidney Disease（CKD）. Damp-heat syndrome is closely related to inflammatory state of the kidney, while Clearing away Heat, Resolving Dampness and Removing Blood Stasis（CRR）Therapy and Qingshen Granule（a Traditional Chinese Medicine having the effect of CRR）can protect vascular endothelial cells and improve renal function through suppressing serum P-selectin and improved NO/ET ratio imbalance in CKD patients, but the signal pathway of P-selectin mediated and its regulation mechanism is not clear. The data have shown that P-selectin and its ligand PSGL-1 could mediated vascular endothelial inflammatory injury and renal fibrosis via the regulation mechanism of MAPK signal pathway. The renal fibrosis model rats of 5/6 nephrectomy and human umbilical vein endothelial cell（HUVEC）injury model induced by Lipopolysaccharides（LPS）are established in this project to study the role of 4 signaling pathways in MAPK family mediated by P-selectin/PSGL-1 on the process of vascular endothelial inflammatory injury and epithelial–mesenchymal transitions（EndMT）, in order to elucidate the mechanism of renal fibrosis from the point of view of vascular endothelial cell injury in, and further observe the the interventional effect of Qingshen Granule on the above signaling transduction and vascular endothelial cell injury, revealing the mechanism of anti-renal fibrosis.