淫羊藿-川芎治疗骨关节炎大鼠的药效学及PK-PD模型研究  

Pharmacodynamics study and establishment of a PK-PD model for Epimedii Folium-Chuanxiong Rhizoma in treating osteoarthritis in rats

作　　者：吴恩慧 章建华[2] 陈文钧 王娅红 尹华[1] WU En-hui;ZHANG Jian-hua;CHEN Wen-jun;WANG Ya-hong;YIN Hua(Research Laboratory for Standardization of Chinese Medicines,School of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 311402,China;Department of Osteopathy and Traumatology,the First Affiliated Hospital of Zhejiang Chinese Medical University,Hangzhou 310006,China)

机构地区：[1]浙江中医药大学药学院中药标准化研究实验室,浙江杭州311402 [2]浙江中医药大学附属第一医院骨伤科,浙江杭州310006

出　　处：《中国中药杂志》2025年第5期1377-1384,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81874340);浙江省科技厅公益性技术应用研究计划项目(2014C33216)。

摘　　要：研究淫羊藿-川芎中各成分的整合药代动力学(PK)和药效动力学(PD)的相关性,阐明淫羊藿-川芎治疗骨关节炎的药效物质基础及作用机制。采用Hulth法建立大鼠骨关节炎模型,各组给药后采集不同时间点血浆,检测多成分的血药浓度;采用酶联免疫吸附法(ELISA)测定血浆中基质金属蛋白酶(matrix metalloproteinase,MMP)-3、MMP-13、白细胞介素-1β(interleukin-1β,IL-1β)、一氧化氮(nitric oxide,NO)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的含量,作为药效学指标。结合权重系数,计算整合PK、PD数据,通过Sigmoid E_(max)拟合模型评价淫羊藿-川芎药对配伍增效作用,进行量-效-时相关性分析。淫羊藿组、川芎组、淫羊藿-川芎组的PK-PD模型分别为E=(1.926×C^(2.652))/(0.1366^(2.652)+C^(2.652))、E=(1.618×C^(345.2))/(0.1184^(345.2)+C^(345.2))、E=(2.305×C^(2.786))/(0.2403^(2.786)+C^(2.786)),淫羊藿-川芎配伍后E_(max)较单用淫羊藿、川芎增大;EC_(50)较单用淫羊藿和川芎加和值减小。MMP-3、MMP-13、IL-1β、NO、TNF-α的浓度与淫羊藿、川芎各成分的质量浓度存在相关性,且配伍优于单用。淫羊藿、川芎、淫羊藿-川芎可能通过抑制炎症因子MMP-3、MMP-13、IL-1β、NO、TNF-α来治疗骨关节炎。This study aims to reveal the correlation between the pharmacokinetics(PK)and pharmacodynamics(PD)of multiple components in Epimedii Folium-Chuanxiong Rhizoma and clarify the pharmacodynamic material basis and mechanism of this herb pair in treating osteoarthritis.The Hulth method was used to establish the rat model of osteoarthritis and plasma was collected at various time points after drug administration.The plasma concentrations of multiple components were measured.Enzyme-linked immunosorbent assay(ELISA)was used to measure the plasma concentrations of matrix metalloproteinase(MMP)-3,MMP-13,interleukin-1β(IL-1β),nitric oxide(NO),and tumor necrosis factor-α(TNF-α)as pharmacodynamic indicators.Self-defined weighting coefficients were used to calculate the PK and PD data,and a Sigmoid E_(max) fitting model was used to evaluate the synergistic effect of the compatibility of Epimedii Folium-Chuanxiong Rhizoma.The PK-PD models for Epimedii Folium,Chuanxiong Rhizoma,and Epimedii Folium-Chuanxiong Rhizoma were E=(1.926×C^(2.652))/(0.1366^(2.652)+C^(2.652)),E=(1.618×C^(345.2))/(0.1184^(345.2)+C^(345.2)),and E=(2.305×C^(2.786))/(0.2403^(2.786)+C^(2.786)),respectively.The E_(max) of Epimedii Folium-Chuanxiong Rhizoma was larger than those of the two herbal medicines alone.The EC_(50) of the herb pair was lower than the sum of Epimedii Folium and Chuanxiong Rhizoma alone.The concentrations of MMP-3,MMP-13,IL-1β,NO,and TNF-α were correlated with mass concentrations of multiple components in Epimedii Folium and Chuanxiong Rhizoma,and the compatibility was better than single use.Epimedii Folium,Chuanxiong Rhizoma,and Epimedii Folium-Chuanxiong Rhizoma may play a role in the treatment of osteoarthritis by inhibiting MMP-3,MMP-13,IL-1β,NO,and TNF-α.

关 键 词：淫羊藿-川芎 骨关节炎 药代动力学-药效动力学模型 药效物质基础 

分 类 号：R285.5[医药卫生—中药学]