川芎嗪醇质体贴片在大鼠体内的药动学以及抗心肌缺血与缺血后再灌注损伤的作用  

Pharmacokinetics of ligustrazine ethosome patch in rats and its effect in anti-myocardial ischemia and anti-ischemic reperfusion injury

作　　者：刘星言[1] 何志巍[1] 李彩虹[1] 曾昭武[1] 刘宏[1] 

机构地区：[1]广东医学院,广东东莞523808

出　　处：《中国现代医学杂志》2012年第13期10-15,共6页China Journal of Modern Medicine

基　　金：2011年广东医学院博士启动项目(No:XB1104)

摘　　要：目的研究川芎嗪醇质体贴片在大鼠体内的药动学以及抗心肌缺血与缺血后再灌注损伤的作用。方法在药动学实验中,雄性SD大鼠随机分为3组:川芎嗪灌胃给药组,川芎嗪醇质体贴片经皮给药组,川芎嗪常规贴片经皮给药组。给药后不同时间取血,并取出心、肝、脾、肺、肾、脑和肌肉等组织,采用HPLC检测药物浓度,计算药动学参数及各组织药物浓度-时间曲线下面积(AUC)值。另外,采用静脉注射垂体后叶素的方法构建大鼠急性心肌缺血的动物模型,采用结扎大鼠冠状动脉左前降支的方法构建心肌缺血再灌注损伤模型,观察川芎嗪醇质体透皮贴片对缺血心肌以及心肌缺血后再灌注损伤的保护作用。结果与川芎嗪灌胃给药组和川芎嗪常规贴片经皮给药组相比,川芎嗪醇质体贴片经皮给药组各组织的AUC值最高。川芎嗪醇质体贴片组的全血黏度、血浆黏度、红细胞压积、红细胞聚集指数、红细胞变形指数较缺血对照组差异有显著性(P<0.01)。另外,川芎嗪醇质体透皮贴片能显著缩小长时间缺血所引起的心肌梗死范围。结论川芎嗪醇质体透皮贴片具有缓释性,给药后能维持稳定、持久的血药浓度,提高生物利用度,减少给药次数。药物贴片组能降低心肌缺血大鼠血液流变学指标,对急性缺血心肌有保护作用,对缺血后再灌注损伤心肌也有一定保护作用。【Objective】 The objective of this study was to investigate the pharmacokinetics of the Ligustrazine ethosome patch and its effect on antimyocardial ischemia and anti-ischemic reperfusion injury.【Methods】 Male Sprague Dawley rats were divided randomly into 3 groups： Group A（intragastric ligustrazine）,Group B（transdermal ligustrazine ethosome patch）,and Group C（conventional transdermal ligustrazine patch）.After treatment,samples of blood and of various tissues such as heart,liver,spleen,lung,kidney,brain,and muscle samples were taken at different time points.Drug concentration was measured with HPLC.Pharmacokinetic parameters and the area under the drug concentration-time curve（AUC） in various tissues were calculated.The rat model of acute myocardial ischemia was constructed with intravenous injection of pituitrin and the model of myocardial ischemia-perfusion injury was constructed by tying off the left anterior descending coronary artery of rats to observe the effect of ligustrazine ethosome patches on ischemic myocardium and ischemia-reperfusion injury.【Results】 Results showed that AUC was highest in the transdermal drug delivery group of ligustrazine ethosome patch.There were significant differences in whole blood viscosity,plasma viscosity,hematocrit,red blood cell aggregation index,and deformation index between ligustrazine the ethosome patch group and ischemic control group（P 〈0.01）.Moreover,ligustrazine ethosome patches could reduce the scope of myocardial infarction induced by long-term ischemia.【Conclusion】 Ligustrazine ethosome patches have a sustained-release property.They can maintain stable and sustained blood drug concentration,increase bioavailability,and reduce administration times.The drug patch can decrease hemorheological indices of myocardial ischemia in rats,as well as protect acute ischemic myocardium and ischemia-reperfusion injured myocardium.

关 键 词：川芎嗪 醇质体 贴片 药动学 心肌缺血 缺血后再灌注损伤 

分 类 号：R-332[医药卫生]