柴黄益肾颗粒是我们在既往基金资助下开发的一个六类中药制剂。药效学结果表明，该药能显著减少糖尿病肾病（DN）模型大鼠肾损伤和尿蛋白排泄。进一步研究发现，模型大鼠早期有机阴离子（OA）尿毒素已经在肾小管上皮细胞显著积聚，且与小管间质损伤程度相关，而柴黄益肾颗粒可以有效降低其积聚水平。肾小管上皮细胞有机阴离子转运蛋白（OATs）是OA尿毒素经肾排泄的重要途径。结合大量文献报道，我们推测糖尿病状态下OATs的异常可能介导了肾小管上皮细胞尿毒素的早期积聚，进而引起DN肾损伤，而柴黄益肾颗粒可能通过调节该途径治疗DN。本课题拟结合体内外实验，阐明肾小管上皮细胞膜上OATs异常/尿毒素积聚途径在DN发生发展中作用，研究柴黄益肾颗粒调控此途径的作用及相关机制，探讨柴黄益肾颗粒治疗DN的作用靶点，为治疗DN的现代中药研究提供科学依据。

Chaihuangyishen(CHYS) granules a new TCM preparation which was developed based on our previous several funds.Our recent studies found that CHYS could ameliorate renal injury and urinary protein in diabetic rats. Further study revealed that in renal tubular epithelial cell of early diabetic model rats, the accumulation of organic anion(OA) toxins has been occurred, which is associated with tubulointerstitial injury and could be effectively reduced by CHYS granules. OA transports in renal tubular epithelial cell is the important pathway of OA uremic toxins excreted from kidney. Based on previous literatures, we speculated that the abnormality of OATs in diabetic condition could mediate the early accumulation of uremic toxins in renal tubular epithelial cell which subsequently induced the kidney damage. We further hypothesize that CHYS granules could improve DN by adjusting this pathway. We plan an experiment to clarify the abnormality of OATS in renal tubular epithelial cell/uremic toxins accumulation pathway in the development of DN, to study the pharmacological mechanism of CHYS granules mediating this pathway, to explore the target of CHYS, to provide the scientific basis for modern TCM treating diabetic nephropathy.