糖尿病肾病(DN)是糖尿病的严重并发症，也是终末期肾病的主要原因，目前尚无有效药物。TLR2/4识别HMGB1而启动炎症反应与DN发生发展密切相关。解毒通络抑制炎症是防治DN的重要策略。前期研究发现，柴胡多糖抑制TLR4通路而降低炎症水平；改善STZ诱导的DN小鼠肾损伤，降低HMGB1表达。由此推测：柴胡多糖通过阻断HMGB1-TLR2/4信号通路治疗DN。本课题拟采用自发和诱导两种DN模型进一步观察柴胡多糖的药效及机制，在分子和细胞水平上，重点观察柴胡多糖对HMGB1表达、分泌及活性的影响，探讨HMGB1作为治疗DN新靶点的可能性；观察柴胡多糖对NF-κB入核的影响，判断其是否独立于对TLR2/4的作用；通过对TLR2 siRNA沉默和对TLR4作用的拮抗，观察柴胡多糖对TLR2和TLR4作用的差异。明确柴胡多糖治疗DN的作用机制，能够为在中药中挖掘DN治疗药物提供新的思路和研究方向。

Diabetic Nephropathy(DN), a type of capillary vessel syndrome, is one of the most common and severe chronic complications of diabetes mellitus. Diabetic nephropathy is the leading cause of end-stage renal disease. There is no effective drug for treating DN. Diabetic nephropathy (DN) is an inflammatory disease. HMGB1 is an endogenous ligand of TLR2/4. HMGB1 mediated TLR2/4 signaling pathway has been confirmed to involve in the pathogenesis of DN. According to integrated traditional Chinese and western medicine theory, JieDuTongLuo and inhibition of inflammation is a new strategy for the treatment of DN. Our previous study found that Bupleurm polysaccharides（BPs）inhibited TLR4 signaling pathway and decreased the level of inflammatory cytokines. BPs improved kidney damage and reduced the expression of HMGB1 in renal tubules in DN mice. We hypothesized that the therapeutic effect of BPs on DN resulted from blocking the HMGB1 mediated TLR2/4 signaling pathway. In this study, both spontaneous and induced DN mice will be used to determine the effect of BPs on DN. We will focus on the effect of BPs on HMGB1 structure, expression, secretion and TLR2/4 binding activity. It is evaluated that HMGB1 might be a new target for DN therapy. To determine whether BPs independent of TLR2/4 signaling pathway exerts its anti-inflammatory activity, the translocation of NF-κB to nuclear is observed. Through siRNA silencing TLR2 and antagonize the effects of TLR4, domination position is evaluated between effect of TLR2 and TLR 4 in DN development. The realization of the mechanism of BPs will be coincidence with the theory of traditional Chinese medicine. This work proposed some potential suggestions for future research and the direction of the investigation. The established reseaching stage will be helpful for new drug discovery by screening from traditional Chinese medicinal materials. Exploring the Inflammatory mechanism of DN by the combination of the traditional and Western medicine, is conducive to give full taking the advantages of traditional Chinese Medicine.