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出 处:《中药新药与临床药理》2013年第6期558-561,共4页Traditional Chinese Drug Research and Clinical Pharmacology
基 金:国家自然科学基金资助项目(81102780)
摘 要:目的考察丹酚酸A(salvianolic acid A,SAA)对大鼠肝脏尿苷二磷酸葡醛酸转移酶(UGTs)的影响。方法SD大鼠48只,雌雄各半,随机分为SAA组、阳性对照组和空白对照组3组。连续给药1周后断头处死动物,分离制备肝组织亚细胞组分,以对硝基酚(4-NP)为探针药物,HPLC法测定各亚细胞组分UGTs活性。结果在不同肝组织亚细胞组分中,以肝微粒体的UGTs酶活性最高,且雄鼠显著高于雌鼠;与空白对照组比较,SAA组大鼠的肝微粒体蛋白浓度和UGTs酶活性均无显著变化,差异无统计学意义(P>0.05)。结论 SAA经静脉途径连续给药1周对SD大鼠肝脏的UGTs酶活性无显著的诱导或抑制作用,提示其在临床应用时发生经UGTs酶介导的药物相互作用的潜在风险较小。Objective To investigate the effect of salvianolic acid A (SAA) on uridine diphosphate glucolactone transferases (UGTs) activity in the liver of SD rats. Methods Forty-eight SD rats were randomly divided into three groups of SAA group, positive control group, and blank control group, 16 animals in each group, half being male. After treatment for one continuous week, the animals were sacrificed, and then liver microsomes, $9 fractions and cytosols were isolated to determine UGTs activity by HPLC method with 4-nitrophenol(4-NP) as a probe drug. Results UGTs activity was much higher in rat livermicrosomes than in cytosols and $9 fractions. Moreover, male rats showed relatively higher UGTs activity in liver microsomes thanfemale ones. When compared with the blank control group, protein concentration and UGTs activity in livermicrosomes of SAA group showed no obvious changes (P 〉 0.05 ). Conclusion Continuous uptake of SAA from intravenous administration for one week has no effect on inducing or inhibiting UGTs activity in rat liver microsomes, suggesting than the potential risk of drug-drug interaction of SAA mediated by UGTs should be low in clinic.
关 键 词:丹酚酸A 尿苷二磷酸葡醛酸转移酶 酶活性 肝微粒体 大鼠
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