摘要
同型半胱氨酸(Hcy)是独立的心血管危险因子,降低Hcy水平有利于减少心血管疾病风险。以大鼠急性蛋氨酸(Met)负荷作为药理模型,就丹参水溶性物质主要活性成分丹酚酸A(SalA)对大鼠血浆中Hcy调节作用进行了药动学和药效学研究,发现1,2.5,5 mg/kg 3个剂量的SalA对Met负荷引起的血浆中总同型半胱氨酸(tHcy)升高有降低作用,并且存在一定的剂量依赖性。本文建立了基于SalA对Hcy调节作用机制的药动学-药效学结合(PK-PD)模型,较好的拟合了药动学和药效学的实验结果,并与丹参素(DSS)对Hcy调节作用的PK-PD模型结果进行比较,定量揭示了SalA对tHcy升高促进作用以及转硫途径消除作用与DSS的差异:SalA对于tHcy上升促进作用弱于DSS,但是对于tHcy转硫途径消除的作用强于DSS。
Elevated plasma total homocysteine（tHcy） level has been acknowledged as an independent risk factor for cardiovascular diseases.Salvianolic acid A（SalA） is one of the major active water-soluble ingredients of Salvia miltiorrhiza.The pharmacokinetics（PK） and pharmacodynamics（PD） of SalA on plasma tHcy in methionine-loading rats was evaluated.Acute treatment with a single dose of SalA（1,2.5,5 mg/kg） in rats with Met loading significantly reduced the plasma tHcy level in a dose-dependent manner.In order to characterize the effect of SalA on plasma tHcy,a mechanism-based PK-PD model was developed.Modeling and simulations well fitted the measured values.By comparison with the PK-PD model of danshensu（DSS）,it was found that the elevated effect of SalA on tHcy by methylation was weaker than that of DSS,while trans-sulfuration promotion effect of SalA on tHcy was greater than that of DSS.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2012年第3期260-265,共6页
Journal of China Pharmaceutical University
