中国中药杂志

2014, v.39(14) 2751-2755

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丹参素在局灶性脑缺血大鼠体内药动学-药效学相关性研究
Study on pharmacokinetics-pharmacodynamics correlation of Danshensu in rats with focal cerebral ischemia

艾进超;周惠芬;舒明春;戴柳玲;郑璐;张宇燕;杨洁红;伍宪彬;万海同;
AI Jin-chao;ZHOU Hui-fen;SHU Ming-chun;DAI Liu-ling;ZHENG Lu;ZHANG Yu-yan;YANG Jie-hong;WU Xian-bin;WAN Hai-tong;Cerebrovascular Disease Research Institute,Zhejiang Chinese Medicine University;Zhejiang Wanli University;

摘要(Abstract):

为探讨丹参素在脑缺血损伤模型大鼠体内的药动学过程及其与抗脑缺血作用的相关性,该文建立了局灶性脑缺血再灌注(MCAO)模型,静脉注射丹参素(40 mg·kg-1)后,采用HPLC-DAD测定不同时间丹参素血药浓度,绘制药-时曲线;同时测定各时间点血浆中超氧化物歧化酶(SOD),乳酸脱氢酶(LDH)活性,绘制时-效曲线;用DAS 3.2.6软件处理数据,并进行相关性分析,比较相同剂量的丹参素给药后在模型及正常大鼠体内的药动学差异以及模型大鼠给药后的药效学指标变化,评价丹参素在治疗脑缺血疾病中的作用。结果,脑缺血再灌注及正常大鼠体内丹参素药动学过程均符合二室模型,主要药动学参数t1/2α分别为(0.267±0.026),(0.148±0.020)h,t1/2β分别为(1.226±0.032),(1.182±0.082)h,AUC0-∞分别为(42.168±4.007),(26.881±1.625)mg·L-1·h,缺血再灌注后大鼠血浆中SOD活性降低,LDH活性升高,丹参素在一定时间内能抑制SOD活性下降,LDH活性上升。表明丹参素在脑缺血再灌注大鼠在体内较正常大鼠体内滞留时间更长,消除减慢,反映了丹参素临床治疗脑缺血疾病的合理性;丹参素抗脑缺血损伤作用可能与其在体内水平有关,其血药浓度与血浆中SOD活性呈正相关,LDH活性呈负相关。
To study the pharmacokinetic process of Danshensu in cerebal ischemia injury model rats and the correlation with its anti-cerebral ischemia effect. In this study,the middle cerebral artery occlusion( MCAO) model was established,in which all of the rats were intravenously injected of Danshensu at a single dose of 40 mg·kg-1. The HPLC-DAD method was applied to determine the plasma concentration of Danshensu at different time points and draw the drug-time curve. Meanwhile,the superoxide dismutase( SOD)and the lactate dehydrogenase( LDH) activity were determined to draw the time-effect curve. The DAS 3. 2. 6 software was used to process the data,analyze their correlation,compare the pharmacokinetic difference between model and normal rats after the administration of the same doses of Danshensu and the changes in pharmacodynamic indicators of model rats after the administration,and evaluate the effect of Danshensu in treating the cerebral ischemia disease. According to the results,the pharmacokinetic processes of Danshensu in the cerebral ischemia-reperfusion and normal rats were consistent to the two-compartment model. The main pharmacokinetic parameters were: t1 /2αwere( 0. 267 ± 0. 026),( 0. 148 ± 0. 020) h; t1 /2βwere( 1. 226 ± 0. 032),( 1. 182 ± 0. 082) h; AUC0-∞were( 42.168 ±4.007),( 26.881 ±1.625) mg·L-1·h. After the cerebral ischemia-reperfusion,the activity of SOD decreased and the activity of LDH increased. Danshensu could inhibit the decrease in the SOD activity and the increase in the LDH activity within a certain period of time. This indicated that Danshensu could stay longer in cerebral ischemia-reperfusion rats than in normal rats and eliminated more slowly,which reflected the rationality of Danshensu in the clinical treatment of cerebral ischemia diseases. Danshensu' s effect against the cerebral ischemic injury may be related with its level in vivo. Its plasma concentration is positively related to the SOD activity and negatively related to the LDH activity.

关键词(KeyWords): 丹参素;药动学;药效学;抗脑缺血损伤
Danshensu;pharmacokinetics;pharmacodynamics;anti-cerebral ischemia injury

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金项目(81173647,81274176);; 浙江省自然科学基金项目(LR12H27001);; 浙江省科技厅项目(2013C33244);; 宁波市自然科学基金项目(2013A610276)

作者(Author): 艾进超;周惠芬;舒明春;戴柳玲;郑璐;张宇燕;杨洁红;伍宪彬;万海同;
AI Jin-chao;ZHOU Hui-fen;SHU Ming-chun;DAI Liu-ling;ZHENG Lu;ZHANG Yu-yan;YANG Jie-hong;WU Xian-bin;WAN Hai-tong;Cerebrovascular Disease Research Institute,Zhejiang Chinese Medicine University;Zhejiang Wanli University;

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