载脂蛋白E基因多态性对氟伐他汀抑制L-02细胞中3-羟基-3-甲基戊二酰辅酶A还原酶活性的影响  

Effect of Apolipoprotein E genetic polymorphism on fluvastatin inhibitory activity of 3-hydroxy-3-methyl glutaric acyl coenzyme A reductase in L-02 cell

作　　者：孙旭[1,2] 罗余萍[2] 熊玉卿[2] 

机构地区：[1]中国食品药品检定研究院国家药物安全评价监测中心药物非临床安全评价研究北京市重点实验室,北京100176 [2]南昌大学医学院临床药理研究所,南昌330006

出　　处：《中国临床药理学杂志》2015年第17期1742-1744,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的考察不同载脂蛋白E基因型存在时,氟伐他汀对L-02细胞3-羟基-3-甲基戊二酰辅酶A（HMG-Co A）还原酶活性的影响。方法建立通过检测还原辅酶（NADPH）反应酶活性的高效液相色谱检测方法及样品处理方法。摸索细胞总蛋白与酶的反应体系,研究氟伐他汀对HMG-Co A还原酶活性的抑制作用。结果建立的高效液相色谱检测方法精密度、准确度及重现性均符合要求。NADPH在2.5~1000.0μmol·L-1线性关系良好。0~5μg·m L-1氟伐他汀对L-02细胞中HMG-Co A还原酶活性的抑制作用成浓度依赖性,最大抑制率为49.73%。载脂蛋白E2、E3、E4分别存在时,氟伐他汀对HMG-Co A还原酶活性的抑制率分别为38.02%,25.12%,21.92%,与野生型E3相比,Apo E2差异有统计学意义（P〉0.05）。结论载脂蛋白E不同基因型存在时,氟伐他汀对L-02细胞HMG-Co A还原酶活性抑制作用有差异。Objective To study the effect of different Apolipoprotein E isoforms on the fluvastatin inhibitory activity of 3- hydroxy- 3- methyl glutaric acyl coenzyme A reductase in L- 02 cells existed.Methods Enzymatic activity was evaluated by determining NADPH using HPLC method after cell sample preparation. Explored the incubation method of protein and hydroxy methylglutaryl coenzyme A reductase inhibitor（ HMG- Co A）,as well as the inhibition effect of fluvastatin in HMG- Co A reductase activities. Results The precision,accuracy and reproducibility of the HPLC method meet the requirements.NADPH in the concentration range of 2. 5- 1000. 0 μmol·L- 1showed good linear relationship. The fluvastatin in the concentration range of0- 5 μg·m L- 1to suppress HMG- Co A reductase activity was concentration dependent and the maximum inhibition rate was 49. 73%.When Apolipoprotein E 2 /3 /4 exsited,the inhibition rate of fluvastatin on HMG- Co A reductase activity were 38. 02%,25. 12%,21. 92%,respectively. Apo E2 showed a siganificant difference with Apo E3.Conclusion The inhibition rate of fluvastatin in HMG- Co A reductase activities in L- 02 with different Apolipoprotein E isoforms were significantly different.

关 键 词：载脂蛋白E 基因多态性 氟伐他汀 L-02细胞 3-羟基-3-甲基戊二酰辅酶A 

分 类 号：R972.6[医药卫生—药品]