丹参酮ⅡA配伍DAPT对肾纤维化过程中Notch1/Jagged1信号途径的干预作用

既往中药配伍抗肾纤维化研究主要局限在中药之间和中药有效组分之间，中西医分子药物之间配伍研究则少见报道，难以反映中西医结合防治肾纤维化的临床实际。新研究发现Notch1/Jagged1信号通路在肾纤维化病理进程中发挥重要作用，γ-分泌酶抑制剂DAPT是Notch信号通路的有效阻滞剂，而丹参脂溶性成分丹参酮ⅡA也具有很好的抗肾纤维化效应。据此，课题组前瞻性地应用DAPT与丹参酮ⅡA配伍，探索其抗肾纤维化的协同作用机制。即采用体内UUO模型和体外肾小管上皮细胞培养相结合的实验方法，从整体、器官、细胞、分子四个水平研究①Notch1/Jagged1信号途径在肾纤维化中的作用；②中药丹参酮ⅡA配伍分子西药DAPT抗肾纤维化的协同效应，对肾小管上皮细胞转化的调节作用。该研究是在课题组丹参组分药对抗肾纤维化研究基础上的深入持续研究，将建立中西医分子药对配伍抗肾纤维化的研究新模式，具有重要的示范研究价值。

Previous the compatibility of traditional Chinese medicine on anti renal fibrosis research mainly confined between traditional Chinese medicine and the components of traditional Chinese Medicine. The study on compatibility of anti renal fibrosis between traditional Chinese medicine and Western medicine molecular drugs is rarely reported，It is difficult to reflect the actual clinical treatment of renal fibrosis with combination of TCM and Western Medicine. Recent evidence suggests that Notch1/Jagged1 signaling pathway play an important role in the process of renal fibrosis, DAPT is an effective γ--secretase inhibitor in Notch signaling pathway. Moreover, Tanshinone II A also has a good effect on anti renal fibrosis. Accordingly, our workgroup use the compatibility of cytokines DAPT and Tanshinone ⅡA prospectively to exploring its synergy mechanism of anti-renal fibrosis. We adopt unique ureteral obstruction animal models in vivo and renal tubular epithelial cell culture methods in vitro investigate the intervention effect of the combination of tanshinone ⅡA and DAPT on Notch1/Jagged1 signaling pathway from the whole、organ、cell、molecule levels. It is the ongoing in-depth study on the basis of Chinese medicine composition against renal fibrosis. At the same time, it will establish a new model of integrative medicine against renal fibrosis and it also plays an important exemplary research value.