基于UPLC/LTQ-Orbitrap-MS技术的复方祖师麻片抗类风湿关节炎的血浆代谢组学研究  

Plasma metabonomic study on Zushima Gancao Tablet in treatment of rheumatoid arthritis based on UPLC/LTQ-Orbitrap-MS

作　　者：彭琳秀 陈良慧[1] 狄留庆[1,2] 单进军[2,3] 谢彤[3] 康安[1,2] 徐牛生 

机构地区：[1]南京中医药大学药学院,江苏南京210023 [2]江苏省中药高效给药系统工程技术研究中心,江苏南京210023 [3]南京中医药大学第一临床医学院,江苏南京210023 [4]赛默飞世尔科技(中国)有限公司,上海201206

出　　处：《中草药》2017年第10期1964-1970,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(81273655);江苏省高校科技成果产业化推进项目(JHB2012-19)

摘　　要：目的分析类风湿关节炎(RA)模型大鼠血浆内源性代谢物的变化,观察复方祖师麻片对异常代谢物的调节作用,从代谢组学的角度探究复方祖师麻片抗RA的作用机制。方法将SD大鼠随机分为对照组、模型组、雷公藤多苷片(阳性药)组和复方祖师麻片组,以弗氏完全佐剂建立佐剂关节炎模型,雷公藤多苷片组和复方祖师麻片组分别ig给予雷公藤多苷片和复方祖师麻片,每天1次,连续31 d,各组分别于造模前及造模后第1、10、20、28天采集血浆样本。采用基于UPLC/LTQ-Orbitrap-MS的代谢组学技术研究各组不同疾病时期代谢物的变化,分析药物的干预机制。结果佐剂型关节炎引起体内氨基酸、脂类等多种代谢物紊乱。复方祖师麻片主要调控了其中12种异常代谢物的水平,对佐剂型关节炎的干预效果良好。结论 RA模型大鼠的多个小分子代谢物偏离正常状态,复方祖师麻片和雷公藤多苷片对模型大鼠干预效果相当,但两者改善异常代谢物的情况不同。复方祖师麻片主要通过下调继发性病变期溶血磷脂酰胆碱(LPC)的水平而达到治疗效果;雷公藤多苷片能有效抑制急性炎症期多种氨基酸代谢异常。Objective To observe the regulating action ofZushima Gancao Tablet on abnormal metabolites by analyzing the changes of endogenous metabolites in plasma of rheumatoid arthritis （RA） rats, and to explore the mechanism of Zushima Gancao Tablet in treating RA from the perspective of metabonomics. Methods Rats were divided into normal group （NG）, model group （MG）, positive medicine group （PMG）, and Zushima Gancao Tablet group （ZGG）. Adjuvant arthritis （AA） rats were established with freund complete adjuvant, rats in PMG and ZGG groups were ig administered with tripterygium glycosides and Zushima Gancao Tablet respectively for a month. Plasma samples were collected on days 1, 10, 20, and 28 before and after administration. UPLC/LTQ-Orbitrap-MS was applied to analyzing the metabolic profile changes of each group in different durations of the disease and mechanism of drug intervention. Results The related pathways of AA mainly involved metabolisms of amino acids, lipids, nucleic acids, and vitamins. Zushima Gancao Tablet had great effect on AA by regulating 12 biomarkers. Conclusion Small molecule metabolites in AA rats are deviated from the normal ones. The effects of Zushima Gancao Tablet and positive medicine （tripterygium polyglycoside） on AA are similar, but the mechanisms were different. Zushima Gancao Tablet down-regulates the level of LPC in secondary lesions while tripterygium polyglycoside tablets could effectively inhibit the metabolisms of a variety of amino acids during acute inflammation.

关 键 词：复方祖师麻片 UPLC/LTQ-Orbitrap-MS 代谢组学 类风湿性关节炎 生物标志物 

分 类 号：R285.5[医药卫生—中药学]