中国中药杂志

2015, v.40(02) 334-338

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基于PK-PD模型研究雷公藤治疗类风湿关节炎生物靶标
Study on biomarker of Tripterygium wilfordii in treatment of rheumatoid arthritis based on PK / PD

刘史佳;戴国梁;孙冰婷;李长印;吴磊;马世堂;居文政;谈恒山;傅海燕;
LIU Shi-jia;DAI Guo-liang;SUN Bing-ting;LI Chang-yin;WU Lei;MA Shi-tang;JU Wen-zheng;TAN Heng-shan;FU Hai-yan;Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;College of Pharmacy of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,General Hospital of Nanjing Military Area Command;Division of Nephrology,Nanfang Hospital,Southern Medical University;

摘要(Abstract):

运用PK-PD模型观察血清样本及雷公藤治疗类风湿关节炎(RA)的抗炎作用,并分别对浓度-时间、效应-时间曲线进行相关分析,采用PCR检测各组大鼠的RORγt,IL-17,STAT3,IL-6 mRNA转录水平。甲氨蝶呤、雷公藤红素和高剂量的雷公藤,均可下调AA大鼠淋巴结中RORγt,IL-17,STAT3,IL-6 mRNA转录水平。根据PK-PD模型研究表明炎症因子与雷公藤的血药浓度存在一定的相关性。雷公藤及其主要活性成分雷公藤红素可通过抑制IL-17细胞因子实现抗炎作用来治疗RA。
To observe the serum samples and the anti-inflammatory effect of Tripterygium wilfordii in treating RA by using the pharmacokinetic-pharmacodynamic model,make a correlation analysis on concentration-time and effect-time curves,and explore RORγt,IL-17,STAT3,IL-6 mRNA transcriptional levels in rats by PCR. Methotrexate,tripterine and high-dose T. wilfordii could down-regulate RORγt,IL-17,STAT3,IL-6 mRNA transcriptional levels in AA rat lymph nodes. The study on PK-PD model showed correlations between inflammatory factors and blood concentration of T. wilfordii. T. wilfordii and its main active constituent tripterine could show the inflammatory effect and treat RA by inhibiting IL-17 cytokine.

关键词(KeyWords): 药动学-药效学模型;IL-17;雷公藤;细胞因子;药代动力学;LC-MS/MS
PK/PD model;IL-17;Tripterygium wilfordii;cytokines;pharmacokinetics;LC-MS/MS

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2012ZX09303009-002);; 江苏高校优势学科建设工程资助项目(2010);; 国家自然科学基金青年科学基金项目(81403174)

作者(Authors): 刘史佳;戴国梁;孙冰婷;李长印;吴磊;马世堂;居文政;谈恒山;傅海燕;
LIU Shi-jia;DAI Guo-liang;SUN Bing-ting;LI Chang-yin;WU Lei;MA Shi-tang;JU Wen-zheng;TAN Heng-shan;FU Hai-yan;Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;College of Pharmacy of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,General Hospital of Nanjing Military Area Command;Division of Nephrology,Nanfang Hospital,Southern Medical University;

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