利用血液代谢组学研究关黄柏生物碱对慢性非细菌性前列腺炎模型大鼠的干预作用  

A Metabolomic Study on the Intervention Effect of Phellodenron Amurense Rupr. Alkaloid Protects Against Chronic Nonbacterial Prostatitis In Rats

作　　者：孙晖[1] 李先娜[1] 张颖[1] 李瑞芳[1] 岳姝崎 张爱华[1] 王喜军[1] 

机构地区：[1]黑龙江中医药大学国家中医药管理局中医方证代谢组学研究中心/国家中医药管理局中药血清药物化学重点研究室/中美中医方证代谢组学技术合作中心,哈尔滨150040

出　　处：《世界科学技术-中医药现代化》2016年第10期1709-1719,共11页Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

基　　金：国家自然科学基金委重点项目(81430093):中药体内药效物质基础的系统分析方法学--中医方证代谢组学研究;负责人:王喜军;科学技术部"重大新药创制"国家科技重大专项(2015ZX09101043-011):中药经典名方整合作用机制关键技术研究;负责人:王喜军;国家自然科学基金面上项目(81173500):基于知柏地黄丸配伍环境的关黄柏治疗肾阴虚相火亢盛的药效物质基础研究;负责人:孙晖

摘　　要：目的:本研究应用行为学、组织病理学和代谢组学技术研究关黄柏生物碱对慢性非细菌性前列腺炎(Chronic Nonbacterial Prostatitis,CNP)的干预作用,从血液代谢组学角度阐释关黄柏生物碱对CNP模型大鼠体内代谢水平的影响及其作用机制。方法:通过对关黄柏进行分离纯化得到含量较高的关黄柏生物碱富集物,采用前列腺注射辣椒素的方法制备CNP模型大鼠,应用UPLC-Triple TOF-MS/MS联用技术建立CNP血液代谢组学研究方法,鉴定CNP生物标记物及代谢通路,确定关黄柏生物碱对CNP干预作用的代谢途径。结果:确定了与CNP密切相关的18个生物标记物及14个代谢通路。关黄柏生物碱通过对花生四烯酸代谢、甘油磷脂代谢、嘌呤代谢等代谢通路的调节,可显著对各项指标及12个CNP生物标记物产生回调作用。结论:关黄柏生物碱可以有效干预CNP的发生与发展,本研究为抗CNP药物的研究与开发提供科学的实验数据。This study aimed to analyze the effecacy of Phellodendron amurense Rupr.（GHB） alkaloid on chronic nonbacterial prostatitis（CNP） in rats. Metabolomic experiments, including behavioral test and tissue pathological approaches were performed to interpret the effectiveness and action of GHB alkaloid against CNP. Through separated and purified GHB alkaloid, a higher concentration of total alkaloid was obtained in this study. CNP model rats were established by means of intraprostatic injection of capsaicin. UPLC-Triple TOF-MS/MS technique was utilized for the establishment of blood metabolomics method of rats, the identification of CNP potential biomarkers and relative pathways. And then the mechanism behind the action of GHB alkaloid against CNP was explained. As a result, 14 potential biomarkers and 14 pathways which were closely related to CNP in aggregate were found out. GHB alkaloid improved the activity scores and the prostate protein exudation of CNP model rats. As the complicated regulation of arachidonic acid metabolism, glycerophospholipid metabolism, purine metabolism and any other pathways, alkaloid succesfully mediated 12 CNP potential biomarkers to the normal levels. In conclusion, it was the first experiment to evaluate the effect and clarify the mechanism behind metabolic pathway of Phellodendron amurense Rupr. alkaloid against CNP, which was proved by the fact that Phellodendron amurense Rupr. alkaloid effectively prevented the development of CNP with the provision of scientific experimental data for anti-CNP drug studies.

关 键 词：关黄柏 生物碱 代谢组学 慢性非细菌性前列腺炎 

分 类 号：R285[医药卫生—中药学]