血脂康抑制猪肝HMG-CoA还原酶的活力  

Xuezhikang inhibits the activity of HMG-CoA reductase in pig liver

作　　者：李鹏[1] 陈兰英[1] 

机构地区：[1]中国医学科学院中国协和医科大学阜外心血管病医院心血管病研究所,北京100037

出　　处：《基础医学与临床》2003年第5期531-534,共4页Basic and Clinical Medicine

摘　　要：为了从酶学实验证实血脂康是羟甲基戊二酸单酰CoA(HMG CoA)还原酶的抑制剂 ,用多次冻融、超离心、硫酸铵分步沉淀及热处理纯化了猪肝HMG CoA还原酶并用分光光度法测其酶活力和反应速度。从 5 0 0g新鲜猪肝组织得到 116mgHMG CoA还原酶粗制品 ,含 10 4活力单位 ,比活力为 89mU mg蛋白。按米氏方程双倒数作图法求得其对底物HMG CoA的米氏常数即Km 为 74 4 μmol L ,其纯度及活力均达到动力学实验要求。利用该酶制品比较了国产降血脂药血脂康与进口降血脂药洛伐他汀及辛伐他汀对HMG CoA还原酶的抑制动力学性质。实验结果显示 ,血脂康与洛伐他汀、辛伐他汀均为HMG CoA还原酶的竞争性抑制剂 ;抑制作用强弱为血脂康 >辛伐他汀 >洛伐他汀 ;其抑制常数Ki分别为 19 9μg mL、2 4 8μg mL和 4 1 6 μg mL。以上表明 ,血脂康对猪肝HMG CoA还原酶有抑制作用 。To prove that Xuezhikang is an inhibitor of the 3 hydroxy 3 methylglutaryl coenzyme A (HMG CoA) reductase based on the enzyme experiments, HMG CoA reductase isolated from fresh pig liver microsomes was purified and activity of HMG CoA reductase was determined. 116mg of crude HMG CoA reductase preparation was obtained from 500g of fresh liver with the specific activity of 89 mU per milligram protein and Km of 74.4μmol/L toward HMG CoA. The purity and activity of the enzyme preparation were high enough to perform the study of inhibitory kinetics. The inhibitory kinetics of Xuezhikang were compared those of with lovastatin and simvastatin. The results showed that all the three were the competitive inhibitors of the HMG CoA reductase. The inhibitory effect of the drugs were ranked as: Xuezhikang > simvastatin > lovastatin, with the Kis of 19.9mg/L?24.8mg/L and 41.6mg/L respectively. It was proved that Xuezhikang inhibited HMG CoA reductase according to results of enzymatic inhibitory kinetics, which provided a scientific explanation of Xuezhikang in reducing blood lipid in clinic.

关 键 词：血脂康 猪 HMG-CoA还原酶活力 抑制动力学 洛伐他汀 辛伐他汀 降血脂药 

分 类 号：R965[医药卫生—药理学]