丹酚酸A、B、C分子药对配伍对肾纤维化过程中PDGF-C/PDGFR-α信号途径的干预作用

丹参及含丹参的中药水煎剂在防治慢性肾脏病的临床实践中被广泛应用，且其传统中医药疗效主要与丹参水溶性活性成分有关，申请人上一个国家自然科学基金研究发现丹参总酚酸有很好的抗肾纤维化疗效，丹酚酸A、B、C是丹参总酚酸的重要组分之一，既往局限于单一组分各自抗肾纤维化研究，难以客观反映丹参多途径、多靶点、多成分的综合效应。据此，课题组选择丹酚酸A、B、C并按比例组成分子药对，采用体内单侧输尿管梗阻（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、分子四个水平研究丹酚酸A、B、C分子药对配伍对血小板源生长因子-C/血小板源生长因子-α受体(PDGF-C/PDGFR-α)信号途径的干预作用，对炎性细胞趋化因子的抑制作用和细胞凋亡相关蛋白的调节作用，将有助于揭示含丹参类水煎剂防治肾纤维化的药效物质基础，为建立中药分子药对配伍延缓慢性肾脏病提供新思路。

Savia miltiorrhiza and herbal decoction which contain it had been widely used in clinical chronic renal disease prevention practice,and its traditional hebal medchine effect depend on its water-solube components.Applicant's previous National Natural Science Foundation subject found that Salvianolic total acid has fabulous anti-fibrosis potential. Salvianolic acid A, B, C, is an important component of salvianolic acids.Respective resisting renal fibrosis study was confined to single herbal medchine component which could't reflect the mutiple pathways、multiple targets、multiple compnents comprehensive effect of Savia miltiorrhiza.Accordingly, our research group chose Salvianolic acid A、B、C compose molecular compatibility according to proportion.To adopt unique ureteral obstruction animal models in vivo and renal tubular epithelial cell culture methods in vitro investigate the intervention effect of Salvianolic Acid A、Salvianolic Acid B、Salvianolic Acid C components compatibilty on (PDGF-C/PDGFR-α)signaling pathway from the whole、organ、cell、molecule levels,and inhibition ability for proinflammatory cytokines and regulation ability for cell apotosis relevant proteins.It will supply theory and experimental evidences for clinical usage of water-soluble components Salvianolic Acid A、B、C coorperation in preventing renal fibrosis.It will help reveal efficacy material basis of Savia miltiorrhiza water decoction and water decoction which contain Savia miltiorrhiza in preventing renal fibrosis.At the same time,it will supply a new insight into delaying chronic renal disease of herbal medchine compotents molecular compatibilty.