丹酚酸A体外葡萄糖醛酸结合代谢种属差异的研究  

Study of Species Differences of Salvianolic Acid A Glucuronidation in Vitro

作　　者：田红翠 李艳丽[1] 江云霞[1] 李方悦 许卉[1] 

机构地区：[1]烟台大学药学院,山东烟台264005

出　　处：《中药新药与临床药理》2014年第4期463-466,共4页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金(81102780);山东省自然科学基金(ZR2013HZ004);烟台大学研究生创新基金(YJSY201423)

摘　　要：目的研究丹酚酸A(salvianolic acid A,SAA)在人和大鼠体外肝微粒体中的葡萄糖醛酸结合代谢反应的种属差异。方法采用人和大鼠肝微粒体体外温孵体系进行SAA的葡萄糖醛酸结合代谢,通过高效液相色谱-质谱联用(HPLC-MS)检测确定产物峰;参考SAA标准曲线计算代谢产物生成量,并通过产物生成量计算酶促动力学参数。结果 SAA在人和大鼠肝微粒体中的葡萄糖醛酸结合代谢均产生4个相同的葡萄糖醛酸结合代谢产物,其最大反应速率(Vmax)分别为0.585,2.08 nmol·min-1·mg-1;米氏常数(Km)分别为0.037,0.065 mmol·L-1。结论 SAA在人和大鼠体外肝微粒体中发生的葡萄糖醛酸结合代谢产物无差异,但酶促反应动力学参数Vmax及Km均有一定的差异,可能与其葡萄糖醛酸转移酶(UGTs)的活性有关。Objective To study the species differences of salvianol ic acid A（SAA） glucuronidati o n in human and rat liver microsomes in vitro. Methods SAA glucuronidation was carried out in human and rat liver microsomes in-vltro warm-incubation system. We confirmed the chromatographic peak of metabolites by using high performance liquid chromatography-mass spectrography（HPLC-MS）, calculated the amount of metabolites by using HPLC-UV, and then got the enzymatic kinetic parameters through the metabolites amount. Results Four glucuronic acid metabolites of SAA were detectable in the human and rat liver microsomes. The maximum reaction rate （Vmax） of glucuronidation was 0.585, 2.08 nmol·min^-1·mg^-1, and Michaelis-Menten constant（K,,）was 0.037, 0.065 mmol·L^-1 in human and rat liver microsomes, respectively. Conclusion SAA glucuronidation metabolites are similar in the human and rat liver microsomes, but enzymatic kinetic parameters of Vmax and Km are different, which is probably related with the activity of their glucuronosyl transferase enzyme（ UGTs ）.

关 键 词：丹酚酸A 葡萄糖醛酸结合 代谢 种属差异 酶促动力学 高效液相色谱-质谱联用 

分 类 号：R285.5[医药卫生—中药学]