加味四妙丸有效部位群抗高尿酸血症作用及其机制  

Effect of active fractions from modified Simiao Wan on hyperuricemia and its mechanism

作　　者：潘红英[1,2] 时乐[2] 徐立[1] 尹莲[2] 曾宛平 张光际 杨凡[2] 

机构地区：[1]南京中医药大学药物安全性评价中心,江苏南京210023 [2]南京中医药大学药学院临床药学系,江苏南京210023

出　　处：《中国药理学与毒理学杂志》2014年第3期380-385,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：江苏省中医药管理局项目(LZ11195);江苏省自然科学基金(BK2002033);江苏省方剂研究重点实验室开放项目(022021014010)~~

摘　　要：目的探讨加味四妙丸(MSW)有效部位群(EFC)对高尿酸血症大鼠血清尿酸水平的影响及其作用机制。方法采用由次黄嘌呤和尿酸酶抑制剂氧嗪酸钾制备持续性大鼠高尿酸血症模型,记录每日摄食量,收集末次造模后12 h尿液,ig给予模型大鼠MSW 50 g·kg-1以及EFC 12.5,25和50 g·kg-1,连续5 d;采用尿酸排泄抑制剂烟酸制备高尿酸血症模型,ig给予模型大鼠MSW 50 g·kg-1以及EFC50 g·kg-1,连续3 d。末次给药后,取血和肝组织。全自动生化仪检测大鼠血清和尿液中尿酸水平,酶比色法测定血清、肝组织中黄嘌呤氧化酶(XOD)、分光光度法检测红细胞、肝组织中嘌呤核苷磷酸化酶(PNP)和尿酸酶等活性。结果与正常对照组相比,2种高尿酸血症模型大鼠血清尿酸水平均明显升高(P<0.01),MSW和EFC 50 g·kg-1均可显著降低2种模型大鼠血尿酸水平(P<0.01)。EFC 12.5和25 g·kg-1可降低由氧嗪酸钾制备的持续性高尿酸血症大鼠血尿酸水平(P<0.05),MSW和EFC各剂量组均可明显升高模型动物红细胞PNP活性(P<0.01),EFC 25和50 g·kg-1还可显著降低血清XOD活性(P<0.05,P<0.01)。对由烟酸复制的大鼠高尿酸血症模型,MSW 50 g·kg-1和EFC 50 g·kg-1均能升高肝组织尿酸酶活性(P<0.05),EFC50 g·kg-1能显著降低模型大鼠血清中XOD活性(P<0.01)。结论 EFC能降低高尿酸血症模型大鼠的尿酸水平,其机制可能与其抑制血清XOD活性使尿酸合成减少以及激活尿酸酶活性促进尿酸分解有关。OBJECTIVE To study the effect of effective fractions（ EFC） from modified Simiao Wan（ MSW） on the level of uric acid in hyperuricemic rats and investigate the mechanism. METHODS Two types of hyperuricemic models were established. A persistant hyperuricemic model was prepared by giving rats oxonic acid 200 mg·kg^-1and feeding them with hypoxanthine. The models were ig given with modified Simiaowan（ MSW） 50 g·kg^-1or EFC 12. 5,25 and 50 g·kg^-1consecutively for 5 d. The models were treated with MSW or EFC 50 g·kg^-1for 3 d. After the final treatment,the uric acid concentrations in serum and urine were determined by an automatic biochemistry analyzer. The activity of xanthine oxidase（ XOD） in the serum and liver was determined by enzymic colorimetric method. The activity of purine nucleoside phosphorylase（ PNP） and uricase was detected by spectrophotometry. RESULTS Compared with normal control group,the serum level of uric acid in both model groups was remarkably increased（ P〈0. 01）. Compared to model control group,MSW 50 g·kg^-1and EFC 12. 5, 25 and 50 g·kg^-1significantly reduced the serum level of uric acid（ P〈0. 05,P〈0. 01）,but increased the activity of erythrocyte PNP（ P〈0. 01） in the oxonic acid potassium-induced hyperuricemia rats. MSW 50 g·kg^-1and EFC 50 g·kg^-1elevated the activity of liver uricase in the nicotinic acid-induced hyperuricemia rats（ P〈0. 05）. EFC 50 g·kg^-1also significantly decreased the serum XOD activity of hyperuricemic rats. CONCLUSION EFC significantly inhibits the serum level of uric acid in hyperuricemic rats,which might involve down-regulation of protein levels of serum XOD to inhibit the production of uric acid and activation of uricase to promote the decomposition of uric acid.

关 键 词：加味四妙方 中草药提取物 高尿酸血症 黄嘌呤氧化酶 嘌呤核苷磷酸化酶 尿酸酶 

分 类 号：R285.5[医药卫生—中药学] R963[医药卫生—中医学]