秦艽地黄通痹汤治疗类风湿关节炎活动期湿热蕴毒证患者血清代谢组学研究  

Serum Metabonomics of Qinjiao Dihuang Tongbi Decoction(秦艽地黄通痹汤)in the Treatment of Active Rheumatoid Arthritis with Damp-heat Toxin Accumulation Syndrome

作　　者：刘欢欢 刘史佳[1] 汪悦[1] 熊玥 鲁璐[1] LIU Huanhuan;LIU Shijia;WANG Yue;XIONG Yue;LU Lu(Affiliated Hospital of Nanjing University of Chinese Medicine,Nanjing,210029;School of Pharmacy,Nanjing University of Chinese Medicine;Jiangsu Quality Inspection and Testing Center for Animal Products)

机构地区：[1]南京中医药大学附属医院,江苏省南京市210029 [2]南京中医药大学药学院 [3]江苏省畜产品质量检验测试中心

出　　处：《中医杂志》2022年第3期245-250,共6页Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81973769);江苏省青年医学重点人才(QNRC2016642);江苏省中医院院级课题(Y19058);江苏高校优势学科建设工程三期项目[苏政办发(2018)87号]。

摘　　要：目的探讨秦艽地黄通痹汤治疗类风湿关节炎活动期湿热蕴毒证的可能作用机制。方法招募类风湿关节炎活动期湿热蕴毒证患者27名,予秦艽地黄通痹汤口服治疗,每日1剂,治疗12周。采用超高效液相色谱串联四极杆飞行时间质谱(UPLC-Q-TOF/MS)检测技术,对类风湿关节炎活动期湿热蕴毒证患者治疗前后血清样本进行分析,再用主成分分析法(PCA)和正交偏最小二乘法判别分析(OPLS-DA)筛选差异性代谢物,并使用MetaboAnalyst网站分析相关代谢通路。结果秦艽地黄通痹汤治疗前后患者血清代谢产物呈现不同的分布,初步鉴定出D-甘露糖、L(-)-阿卓糖、棕榈酸、硬脂酰胺、半乳糖醇和油酰磷酸胆碱6个差异代谢物。与治疗前比较,类风湿关节炎活动期湿热蕴毒证患者血清D-甘露糖、L(-)-阿卓糖、棕榈酸和油酰磷酸胆碱含量下降,硬脂酰胺和半乳糖醇含量上升(P<0.05)。共鉴定出7个代谢通路,包含半乳糖代谢、甘油脂代谢、果糖和甘露糖降解、线粒体中的脂肪酸延伸、脂肪酸生物合成、脂肪酸代谢、胆汁酸生物合成,其中与差异代谢物相关性较强的是半乳糖代谢通路(P<0.05),匹配半乳糖醇和D-甘露糖差异代谢物。结论秦艽地黄通痹汤治疗类风湿关节炎活动期湿热蕴毒证可能与激活肝脏中的半乳糖代谢途径而间接改善能量代谢过程有关。Objective To explore the possible mechanism of Qinjiao Dihuang Tongbi Decoction(秦艽地黄通痹汤,QDTD)in the treatment of active rheumatoid arthritis(RA)with damp-heat toxin accumulation syndrome.Methods Twenty-seven patients with active RA and damp-heat toxin accumulation syndrome were included to be treated with oral QDTD,one dose daily,for 12 weeks.The serum samples collected from patients before and after treatment with QDTD were analyzed using ultra performance liquid chromatography-quadrupole time-of-flight/mass spectrometry(UPLC-Q-TOF/MS).Principal components analysis(PCA)and orthogonal partial least squares-discrim⁃inant analysis(OPLS-DA)were performed to screen differential metabolites,and MetaboAnalyst website was used to analyze the relevant metabolic pathways.Results The serum metabolites were presented in different distributions before and after the treatment of QDTD,and six differential metabolites including D-mannose,L(-)-altrose,palmitic acid,stearamide,galactitol and oleoyl phosphocholine were initially identified.Compared to those before treatment,the serum D-mannose,L(-)-altrose,palmitic acid and oleoyl phosphocholine decreased after treatment,and the stea⁃ramide and galactitol levels increased(P<0.05).Seven metabolic pathways were identified,which were galactose metabolism,glycerolipid metabolism,fructose and mannose degradation,fatty acid extension in mitochondria,fatty acid biosynthesis,fatty acid metabolism,and bile acid biosynthesis.Among them,the galactose metabolism pathway was significantly correlated with the differential metabolites galactitol and D-mannose(P<0.05).Conclusion QDTD may play its role in the treatment of active RA with damp-heat toxin accumulation syndrome by activating the galactose metabolism pathway in the liver and indirectly improve the energy metabolism process.

关 键 词：类风湿关节炎 湿热蕴毒证 秦艽地黄通痹汤 代谢组学 超高效液相色谱-质谱 

分 类 号：R259[医药卫生—中西医结合]