基于多维谱效与入血成分分析的大果飞蛾藤治疗急性痛风性关节炎药效物质辨识和作用机制研究

Acute gouty arthritis patients, which contribute to the majority of those with gout, suffer from repeated attack of pain, and could be easily disabled, teratogenic if not treated effectively. Traditional Chinese Medicine (TCM) has long been used for the prevention and treatment of gout. The abundance in theory and herbs on the treatment of gout make it great significant and prospective for further research and development of effective TCM. The Caulis of Erycibe obtusifolia and Erycibe schmidtii are officially recorded in the Chinese Pharmacopoeia (2015) under the same name, Erycibes Caulis. With the reduction of the wild E. obtusifolia and E. schmidtii resources, Porana sinensis has been widely used as the substitute. Previously studies indicated that P. sinensis could reduce the serum uric acid level and inhibit xanthine oxidase activity in the liver of rats hyperuricemic model. In this study, multi-dimensional spectrum-effect relationship and analysis of the absorbed components in serum will be carried out to clarify the efficacy material base of P. sinensis on the treatment of acute gouty arthritis. Both in vivo and in vitro experiments will be conducted to clarify the multi-target mechanism of P. sinensis on the treatment of acute gouty arthritis. The research results is prospected to provide evidence to support the clinical use for P. sinensis on the treatment of acute gouty arthritis and expand medicinal plant resources.

急性痛风性关节炎患者疼痛反复发作，在就诊的痛风患者中所占比例最大，如不积极治疗极易致残、致畸形。中医药防治痛风由来已久，有着丰富的理论和有效方药，对有效的抗痛风中药进行进一步的研究、开发具有重要意义。丁公藤（Erycibe obtusifolia）和光叶丁公藤（Erycibe schmidtii）的藤茎为2015版《中国药典》载丁公藤的正品。随着丁公藤和光叶丁公藤野生药用资源的减少，大果飞蛾藤（Porana sinensis）实际上已经成为市场上主流代用品。前期的研究结果表明大果飞蛾藤具有抗炎、镇痛药效，能够有效降低大鼠高尿酸血症模型中血尿酸浓度和肝脏黄嘌呤氧化酶活性。基于此本研究拟引入多维谱效和入血成分分析的方法研究大果飞蛾藤治疗痛风性关节炎的药效物质，应用体内外实验研究大果飞蛾藤治疗痛风性关节炎多靶点作用机制。本研究有望为大果飞蛾藤治疗痛风性关节炎的应用提供支持，拓展中药药用资源。

急性痛风性关节炎如不积极治疗极易致残、致畸形，影响关节功能。中医药在防治痛风方面有着丰富的理论及许多有效方药，对有效的抗痛风中药进行进一步的研究、开发具有重要意义。前期的研究结果表明大果飞蛾藤具有抗炎、镇痛药效，能够有效降低大鼠高尿酸血症模型中血尿酸浓度和肝脏黄嘌呤氧化酶活性。基于此本研究引入多维谱效和入血成分分析的方法研究大果飞蛾藤治疗痛风性关节炎的药效物质。应用网络药理学结合实验验证研究大果飞蛾藤治疗痛风性关节炎多靶点作用机制。同时，建立大果飞蛾藤质量控制方法提升其质量控制水平。采用高分辨质谱鉴别方法鉴别了大果飞蛾藤中18个化学成分和13个代谢产物。结合谱效关系研究，最终选取8个成分用于大果飞蛾藤质量控制。网络药理学研究结果表明香豆素类和绿原酸类为大果飞蛾藤治疗急性痛风性关节炎主要药效物质。大果飞蛾藤通过调控PI3K-Akt，MAPK，NF-kappa B和toll-like receptor等信号通路发挥抗痛风作用。动物实验结果表明大果飞蛾藤提取物能显著抑制TLR2和MyD88 mRNA表达，降低脂质过氧化，调节IL-1β，IL-4和TGF-β释放。本项目系统阐释了大果飞蛾藤治疗急性痛风性关节炎药效物质和多靶点作用机制，为大果飞蛾藤在治疗急性痛风性关节炎领域的临床应用提供了实验支持。

内容获取失败，请点击重试