芦荟大黄素在小鼠体内的药代动力学及组织分布特征研究
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摘要
目的:建立小鼠血浆和组织中芦荟大黄素的含量测定方法,研究芦荟大黄素在小鼠体内的药代动力学及组织分布。方法:小鼠灌胃给予52. 2、26. 1、13. 05 mg/kg浓度芦荟大黄素后,采集血浆及组织样品,经固相萃取法处理后用高效液相色谱-荧光检测器(HPLC-FLD)测定芦荟大黄素浓度。采用Venusil XBP C18(L)(4. 6 mm×250mm,5μm)色谱柱,流动相为甲醇-0. 1%磷酸水(75∶25),柱温30℃,激发波长:435nm,发射波长:515nm。结果:在小鼠血浆和组织中,芦荟大黄素浓度在0. 0114μg/ml～3. 420μg/ml范围内呈现良好的线性关系(r均大于0. 99),日内、日间精密度RSD均小于15%,准确度在85. 9%～104. 4%范围内,芦荟大黄素在小鼠组织中的分布情况为:芦荟大黄素在胃、肠都有较好的吸收。芦荟大黄素因具有脂溶性较好的特性,在脂肪的分布相对较高。组织分布研究发现芦荟大黄素在肝、肾、小肠中的浓度明显高于血液。结论:本实验建立的HPLC-FLD操作简便、精密度高,适用于芦荟大黄素在小鼠体内的药代动力学和组织分布研究,为芦荟大黄素作用机制研究提供参考。
Objective: To establish a method for quantitative analysis of aloe-emodin in plasma and tissues of mice,and study the pharmacokinetics and tissue distribution of aloe-emodin. Methods: After intragastrically administered of aloe-emodin at doses of 52. 2 mg/kg,26. 1 mg/kg and13. 05mg/kg,plasma and tissues of mice were collected. After prepared with solid phase extraction,aloe-emodin was determined by HPLCFLD. Chromatographic separation was carried out on a Venusil XBP C18( L)( 4. 6 mm × 250 mm,5μm) column with the column temperature on 30℃,and the mobile phase was consisted of methanol-0. 1% phosphoric acid in water( 75: 25) at a flow rate of 1. 0 ml/min. The excitation wavelength and emission wavelength were 435 nm and 515 nm. Results: In mouse plasma and tissue,the concentration of aloe emodin in 0. 0114-3. 420μg/ml showed a good linear relationship( R greater than 0. 99). The RSDs of intra-day and inter-day were both lower than 15%,the accuracy was in the range of 85. 9%-104. 4%. The distribution of aloe-emodin in the tissue showed that it was well absorbed in the stomach and intestine. It also had the high distribution in fat because of its good fat-soluble property. Tissue distribution studies found that the concentrations of aloe-emodin in the liver,kidney and small intestine were significantly higher than that in the blood. Conclusion: A simple and accurate method is developed and applied to pharmacokinetic and tissue distribution of aloe-emodin in mice which can provide reference for the study of the mechanism of aloe-emodin.
Objective: To establish a method for quantitative analysis of aloe-emodin in plasma and tissues of mice,and study the pharmacokinetics and tissue distribution of aloe-emodin. Methods: After intragastrically administered of aloe-emodin at doses of 52. 2 mg/kg,26. 1 mg/kg and13. 05mg/kg,plasma and tissues of mice were collected. After prepared with solid phase extraction,aloe-emodin was determined by HPLCFLD. Chromatographic separation was carried out on a Venusil XBP C18( L)( 4. 6 mm × 250 mm,5μm) column with the column temperature on 30℃,and the mobile phase was consisted of methanol-0. 1% phosphoric acid in water( 75: 25) at a flow rate of 1. 0 ml/min. The excitation wavelength and emission wavelength were 435 nm and 515 nm. Results: In mouse plasma and tissue,the concentration of aloe emodin in 0. 0114-3. 420μg/ml showed a good linear relationship( R greater than 0. 99). The RSDs of intra-day and inter-day were both lower than 15%,the accuracy was in the range of 85. 9%-104. 4%. The distribution of aloe-emodin in the tissue showed that it was well absorbed in the stomach and intestine. It also had the high distribution in fat because of its good fat-soluble property. Tissue distribution studies found that the concentrations of aloe-emodin in the liver,kidney and small intestine were significantly higher than that in the blood. Conclusion: A simple and accurate method is developed and applied to pharmacokinetic and tissue distribution of aloe-emodin in mice which can provide reference for the study of the mechanism of aloe-emodin.
引文
[1]李牧,杜智敏.芦荟大黄素的药理作用研究进展.中国临床药理学杂志,2015,31(9)∶765~768.
[2]米丽,李敬超,张夏华,等.番泻叶的化学成分和药理作用研究进展.西南军医,2009,11(4)∶727~728.
[3]熊兴富.中药大黄主要有效成分药理学研究进展.中医临床研究,2014,6(10)∶143~146.
[4]李月珍,刘志新,蔡克瑞,等.高浓度芦荟大黄素诱导胃癌细胞凋亡的作用.中华肿瘤防治杂志,2010,17(12)∶908~911.
[5]张莹莹,周培,王炳芳.芦荟大黄素对小鼠非酒精性脂肪性肝炎的治疗作用.江苏大学学报(医学版),2016,26(4)∶283~287.
[6]Vargas F,Fraile G,Velasquez M,et al. Studies on the photosta-bility and phototoxicity of aloe-emodin,emodin and rhein. Pharmazie,2002,57(6)∶399~404.
[7]冯素香,李晓玉,周悌强,等. HPLC-UV与HPLC-FLED对比分析大黄药材中蒽醌类成分的含量.中国实验方剂学杂志,2015,21(3)∶70~74.
[8]晋齐中,汪宁,刘亚芳.中药生物样品分析前处理方法研究.亚太传统医药,2014,10(4)∶67~69.
[9]冯素香,徐会平,李建生,等.大鼠血浆中芦荟大黄素浓度的固相萃取-高效液相色谱法测定及其药代动力学研究.中国新药杂志,2012,21(8)∶908~911.
[10]朱成琳,张丹参,宋金艳,等.三种大黄酚制剂在小鼠体内的组织分布研究.中国药学杂志,2012,47(11)∶898~902.
[11]张洪,闫士君,张福明.大黄素固体脂质纳米粒在小鼠体内的组织分布研究.中国药房,2012,23(7)∶583~586.
[12]王磊,张静泽,高文远.大黄活性成分药代动力学研究进展,中成药,2011,33(9)∶1571~1574.
[2]米丽,李敬超,张夏华,等.番泻叶的化学成分和药理作用研究进展.西南军医,2009,11(4)∶727~728.
[3]熊兴富.中药大黄主要有效成分药理学研究进展.中医临床研究,2014,6(10)∶143~146.
[4]李月珍,刘志新,蔡克瑞,等.高浓度芦荟大黄素诱导胃癌细胞凋亡的作用.中华肿瘤防治杂志,2010,17(12)∶908~911.
[5]张莹莹,周培,王炳芳.芦荟大黄素对小鼠非酒精性脂肪性肝炎的治疗作用.江苏大学学报(医学版),2016,26(4)∶283~287.
[6]Vargas F,Fraile G,Velasquez M,et al. Studies on the photosta-bility and phototoxicity of aloe-emodin,emodin and rhein. Pharmazie,2002,57(6)∶399~404.
[7]冯素香,李晓玉,周悌强,等. HPLC-UV与HPLC-FLED对比分析大黄药材中蒽醌类成分的含量.中国实验方剂学杂志,2015,21(3)∶70~74.
[8]晋齐中,汪宁,刘亚芳.中药生物样品分析前处理方法研究.亚太传统医药,2014,10(4)∶67~69.
[9]冯素香,徐会平,李建生,等.大鼠血浆中芦荟大黄素浓度的固相萃取-高效液相色谱法测定及其药代动力学研究.中国新药杂志,2012,21(8)∶908~911.
[10]朱成琳,张丹参,宋金艳,等.三种大黄酚制剂在小鼠体内的组织分布研究.中国药学杂志,2012,47(11)∶898~902.
[11]张洪,闫士君,张福明.大黄素固体脂质纳米粒在小鼠体内的组织分布研究.中国药房,2012,23(7)∶583~586.
[12]王磊,张静泽,高文远.大黄活性成分药代动力学研究进展,中成药,2011,33(9)∶1571~1574.