基于NF-κB/Nrf2信号通路和脂质组学技术探讨猪苓的利尿物质基础抗肾纤维化的机制

慢性肾功能衰竭（CRF）是影响人类健康的重要疾病之一。肾间质纤维化是CRF的主要病理特征，如何利用药物干预肾间质纤维化的发展是防治CRF的关键。我们曾研究并初步发现猪苓的正己烷萃取物和麦角甾酮分别是猪苓的利尿活性部位和活性成分，且进一步发现麦角甾酮对腺嘌呤诱导的CRF与马兜铃酸肾病均有较好的防治效果。本课题拟在此初步的研究基础上，采用腺嘌呤诱导的CRF大鼠模型，应用药理学和脂质组学较深入地研究：1）猪苓的正己烷萃取物和麦角甾酮对CRF防治效果；2）探索正己烷萃取物及麦角甾酮对CRF大鼠NF-κB/Nrf2和TGF-β/Smad信号通路在肾脏表达的干预作用；3）基于脂质组学技术鉴定脂质类生物标示物，揭示它们抗肾间质纤维化的生物化学机制。阐明猪苓的正己烷萃取物和麦角甾酮如何干预上述信号通路的蛋白表达与脂质类生物标示物的代谢，为揭示猪苓抗肾间质纤维化的药效物质基础及作用机制提供一定的参考依据。

Chronic renal failure (CRF) is one of the important diseases for human health. Renal interstitial fibrosis is the main pathologic feature of CRF. How to improve progressive renal interstitial fibrosis by drug is very important to treatment of the progressive CRF. Our previous study found that n-hexane extraction and ergone were diuretic bioactive fraction and bioactive fraction of Polyporus umbellatus respectively and the diuretic component ergone can treat adenine-induced CRF and renal interstitial fibrosis of aristolochic acid nephropathy. Based on our previous studies, this project will foucs on adenine-induced CRF model using pharmacology and lipidomics methods. The objective of the current effort was 1) to perform on therapeatic effect of diuretic fraction n-hexane extraction and diuretic component ergone on adenine-induced CRF rats; 2) to explore the molecular mechanism of n-hexane extraction and ergone on renal tissue NF-κB/Nrf2 and TGF-β/Smad pathways in CRF rats; 3) to identified endogenous lipid biomarkers by lipidomics to uncover the biochemical mechansim of their protective effects on renal interstitial fibrosis. This study will illuminate the intervention effects of n-hexane extraction and ergone from Polyporus umbellatus on above-mentioned macromolecular protein signal pathways and endogenous lipid biomarkers. This study will clarify their action mechanism against renal interstitial fibrosis and provide a reference for material basis of effective components of Polyporus umbellatus against renal interstitial fibrosis.