利用中效原理评价虎杖苷与大黄素配伍对高尿酸血症模型大鼠的保护作用  

Protective Effect of Polydatin Complicated with Emodin on Hyperuricemia Model Rats with Median Effect Principle

作　　者：张怡 杨馨悦 屈勇 陈运中 ZHANG Yi;YANG Xinyue;QU Yong;CHEN Yunzhong(School of Pharmacy,Hubei University of Traditional Chinese Medicine,Wuhan 430065,China;Dept.of Pharmacy,CR&WISCO General Hospital,Wuhan 430080,China)

机构地区：[1]湖北中医药大学药学院,武汉430065 [2]华润武钢总医院药学部,武汉430080

出　　处：《中国药房》2020年第21期2603-2608,共6页China Pharmacy

基　　金：国家重点研发计划中医药现代化研究重点专项(No.2017YFC1701003)。

摘　　要：目的:研究虎杖苷与大黄素配伍对高尿酸血症(HUA)模型大鼠的保护作用,筛选两者最优配伍比例,并探讨其可能机制。方法:将SD大鼠随机分为正常对照组、模型组、苯溴马隆组(阳性对照,8 mg/kg)、虎杖苷单用组、大黄素单用组和两药合用A、B、C组,每组各剂量均设置5只大鼠。正常对照组和模型组大鼠均灌胃等体积0.3%羧甲基纤维素钠溶液,各给药组大鼠灌胃相应药物,灌胃体积均为0.1 m L/10 g,每日1次,连续7 d。除正常对照组外,其余各组大鼠均于末次给药1 h前单次腹腔注射氧嗪酸钾(300 mg/kg)以复制HUA模型。末次给药1 h后,检测正常对照组、模型组、苯溴马隆组以及虎杖苷单用组、大黄素单用组(剂量均分别为0.625、1.25、2.5、5、10 mg/kg)和合用A组[虎杖苷+大黄素剂量分别为(0.625+0.625)、(1.25+1.25)、(2.5+2.5)、(5+5)、(10+10)mg/kg]大鼠血清中尿酸的含量;利用中效原理计算上述单用组和合用组的效应(Fa)和联合指数(CI),绘制两成分单用及合用的量效关系曲线以及经模拟后的Fa-CI曲线,评价两药的合用效果。同法检测单用组和合用B、C组[虎杖苷+大黄素剂量分别为(0.625+0.625)、(0.625+1.25)、(0.625+2.5)、(0.625+5)、(0.625+10)mg/kg和(0.625+0.625)、(1.25+0.625)、(2.5+0.625)、(5+0.625)、(10+0.625)mg/kg]大鼠血清中尿酸的含量并计算Fa值,筛选两药的最佳配伍比例。检测正常对照组、模型组、苯溴马隆组以及虎杖苷、大黄素单用组(剂量均为10 mg/kg)和最佳配伍比例合用组大鼠血清中黄嘌呤氧化酶(XOD)的含量,初步分析其作用机制。结果:与正常对照组比较,模型组大鼠尿酸含量显著升高(P<0.01)。与模型组比较,除虎杖苷单用0.625 mg/kg组外,其余各给药组大鼠尿酸含量均显著降低(P<0.05或P<0.01)。两药单用及合用时,其Fa值均与药物剂量成正相关(截距>0,相关系数>0.9),且合用组的Fa值高于任一药物单用组;当模拟Fa值>15%时OBJECTIVE:To study the protective effect of polydatin complicated with emodin on hyperuricemia(HUA)model rats,and to screen the optimal complication proportion and investigate the potential mechanism.METHODS:SD rats were randomly divided into normal control group,model group,benzbromarone group(positive control,8 mg/kg),polydatin alone group,emodin alone group and drug combination group A,B,C,with 5 rats in each group of each dosage.Normal control group and model group were given constant volume of 0.3%CMC-Na solution,administration groups were given relevant medicine intragastrically.Each group was given 0.1 m L/10 g intragastrically once a day,for consecutive 7 d.Expect for normal control group,other groups were given intraperitoneal injection of potassium oxonate 300 mg/kg 1 h before last medication to induce HUA model.One hour after last medication,the serum contents of uric acid(UA)were determined in normal control group,model group,benzbromarone group,polydatin/alone group(0.625,1.25,2.5,5,10 mg/kg)and drug combination group A[the dose of polydatin+emodin were(0.625+0.625),(1.25+1.25),(2.5+2.5),(5+5),(10+10)mg/kg].The effect(Fa)and combination index(CI)of above single drug groups and combination groups were calculated by the median effect principle.The dose-effect relationship curves of two components alone or combination were drawn;Fa-CI curves after simulation were also drawn to evaluate the effect of two-drug combination.Serum contents of UA in rats were determined and Fa value was calculated in single drug groups and drug combination group B,C[the dose of polydatin+emodin were(0.625+0.625),(0.625+1.25),(0.625+2.5),(0.625+5),(0.625+10)mg/kg and(0.625+0.625),(1.25+0.625),(2.5+0.625),(5+0.625),(10+0.625)mg/kg].The optimal complication proportion of two drugs were screened.The serum contents of xanthine oxidase(XOD)in rats were determined in normal control group,model group,benzbromarone group,polydatin/emodin alone group(10 mg/kg)and the optimal complication proportion groups.The mechanism was analyzed pri

关 键 词：虎杖苷 大黄素 中效原理 高尿酸血症 协同效应 黄嘌呤氧化酶 作用机制 大鼠 

分 类 号：R965.1[医药卫生—药理学]