基于均匀设计的降尿酸方最佳配伍及其抗小鼠高尿酸血症效应研究

Optimized Compatibility of "Jiangniaosuan Prescription" and Its Therapeutic Effect on Hyperuricemia in Mice:a Study Based on Uniform Design

目的:探索以"清热祛湿、补肾通络"为治法的降尿酸方主效应中药最佳配伍及其可能的降尿酸机制。方法:以氧嗪酸钾250 mg/kg腹腔注射诱导昆明小鼠高尿酸血症模型,对降尿酸方中肉桂、黄柏、秦皮、桑寄生4味中药根据均匀设计U9(96)表分组实验,以血尿酸为考察指标,用逐步回归分析法筛选最佳配伍;以血清黄嘌呤氧化酶(XOD)及肾脏尿酸转运蛋白URAT1、OAT1、OAT3为靶点,检测最佳配伍组可能的降尿酸机制,并以苯溴马隆为阳性对照进行效应验证。结果:回归方程提示,降尿酸方中黄柏、秦皮、桑寄生组合且其生药剂量分别为50、260、50 mg/kg时降尿酸效果最佳;该配伍组可明显抑制XOD的生物合成,上调rOAT1、rOAT3蛋白与下调rURAT1蛋白表达。结论:该筛选结果可靠,且其作用机制可能与抑制XOD的生物合成及其上调rOAT1、rOAT3蛋白表达及下调rURAT1蛋白表达相关。

Objective： To explore the optimized compatibility of ＂Jiangniaosuan Prescription＂ and its therapeutic effect on hyperuricemia by ＂clearing heat to expel dampness,nourishing kidney to dredge collaterals＂.Methods： The hyperuricemia models were established by injecting 250 mg/kg Oteracil potassium intraperitoneally.Depending on the uniform design graph U9（96）,we design the divided experiments of the 4 ingredients in ＂Jiangniaosuan Prescription＂ by observing the blood uric acid index.We selected the optimized compatibility by regression analysis method;the mechanism of decreasing uric acid in the optimized compatibility group was detected by positive controlling the benzbromarone,and the target spots are XOD,URAT1,OAT1,OAT3.Results： The regression analysis showed that Cortex Phellodendri,Cortex Fraxini and Herba Taxilli in ＂Jiangniaosuan Prescription＂ are the best compatibilities when their doses are 50,260,50 mg/kg respectively.This compatibility of medicines can inhibit the biosynthesis of XOD,up-regulate the expression of protein rOAT1 and rOAT3 and down-regulate the expression of rURAT1 protein.Conclusion： The screening results are reliable,the main mechanism may be associated with the inhibition of XOD biosynthesis,up-regulation of the rOAT1 and rOAT3 expression,down-regulation of rURAT1 expression.