广金钱草调控吲哚胺双加氧酶延缓草酸钙结晶肾损伤的机制研究

Urinary calculi, whose incidence increased year by year, has become an important cause of chronic kidney disease. And the crystal induced renal tubluar injury is the key pathogenesis basis of the disease. Desmodium styracifolium against urinary calculi is an important genuine material of Chinese traditional medicine, however, the mechanism of anti-crystal and protecting tubular epithelial cell remain unclearly. Our previous research used the modern phytochemical means to separate and extract different parts from desmodium styracifolium, and found that the ethyl acetate part is the active site who has a better effect on antagonisting kidney injury induced cryatallization in vitro and in vivo. On this basis, we use metabolomics methods to find tryptophan metabolic disorder during the process of kidney injury, but the ethyl acetate part is just able to regulate the phenomenon. So our research team make some strategies targeting metabolism quantitative and network pharmacology and so on, establish links between compounds and the key enzyme-indolamine dideoxy enzyme IDO in the tryptophan/kynurenine metabolism pathway on the basis of clear compounds substance in the ethyl acetate part. Then we conduct intensive research, a detailed discussion of molecular mechanism that Desmodium styracifolium active site regulate IDO and related signaling pathway, in the hope of elucidating the protective effects of Desmodium styracifolium on renal injury induced by crystal, and providing necessary theotical basis and reference for drug development.

泌尿系结石发病率逐年升高，已成为慢性肾脏病的重要病因，而结晶造成的小管上皮损伤是这一过程的重要病理基础。广金钱草是我国传统医学中重要的对抗泌尿系结石的道地药材，但对其拮抗结晶生成、保护小管上皮细胞的作用机理尚未完全阐释明了。课题组前期利用现代植物化学手段分离提取了广金钱草不同部位并发现正丁醇提取物部位具有较好的体内外抗结晶诱导的肾损伤作用，是广金钱草发挥药效的活性部位。在此基础上，利用代谢组学方法发现结晶肾损伤过程中机体存在色氨酸代谢异常，而正丁醇提取物可以调控这一代谢异常。为此课题组利用靶向代谢定量、网络药理学等研究策略，在明确正丁醇提取物中化学物质基础上，建立了化合物同色氨酸/犬尿氨酸代谢通路中关键酶-吲哚胺双脱氧酶IDO的联系。并基于此开展深入研究，详细探讨广金钱草活性部位调控IDO的分子机制及相关信号通路，以期为阐明广金钱草对结晶肾损伤的保护作用，进行药物开发提供必要的理论依据。