摘要
目的研究芍药苷的大鼠小肠吸收,探讨芍药苷的吸收机制及其影响因素。方法使用高效液相色谱-质谱联用技术,采用肠外翻模型,测定不同质量浓度芍药苷溶液在大鼠空肠和回肠的吸收,同时观察加入聚山梨醇酯-80和P-糖蛋白抑制剂维拉帕米对芍药苷吸收的影响。结果在20～120mg·L-1内,芍药苷吸收未饱和,呈线性吸收,在低质量浓度下空肠与回肠吸收速率无明显差异,中、高质量浓度时回肠吸收速率要高于空肠,2g·L-1的聚山梨醇-80对空肠吸收有促进作用,维拉帕米对芍药苷吸收有显著促进作用。结论芍药苷在小肠外翻模型中吸收遵循一级动力学,芍药苷在不同肠段的吸收有差异,芍药苷是P-糖蛋白的底物,聚山梨醇-80有利于提高芍药苷的吸收。
Abstract
OBJECTIVE To study the absorption of paeoniflorin in the small intestines of rat,and discuss the metabolism and the influence factors of absorption. METHODS The rat jejunum and ileum were incubated with different concentrations of paeoniflorin solution respectively,and the absorption of paeoniflorin in different models was determined by high performance liquid chromatography with mass detector (HPLC-MS). The influence on the absorption of paeoniflorin was investigated after adding Tween-80 and Verapamil,a p-glycoprotein inhibitor.RESULTS When the concentration was from 20 to 120 mg·L-1,the uptake of paeoniflorin increased linearly and did not appear to be saturated. There wasn′t significant difference in the permeability coefficient between the jejunum and ileum at low concentration,but the latter was higher than the former at middle and high concentration. Tween -80 enhanced the absorption of paeoniflorin in jejunum,and Verapamil showed effect on increasing the absorption of paeoniflorin remarkably. CONCLUSION The absorption of paeoniflorin is different in the diverse intestinal segments,and is accorded with first-order kinetics. Paeoniflorin is the substrate of p-glycoprotein. Tween-80 can enhance the absorption of paeoniflorin.
关键词
芍药苷 /
小肠吸收 /
液质联用
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Key words
paeoniflorin /
small intestine absorption /
HPLC-MS
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水文波;贺庆;葛志伟;程翼宇.
高效液相色谱-质谱联用法研究芍药苷的大鼠小肠吸收[J]. 中国药学杂志, 2007, 42(14): 1098-1100
SHUI Wen-o;HE Qing;GE Zhi-wei;CHENG Yi-yu.
Studies on Absorption of Paeoniflorin in Rat Small Intestines by HPLC-MS [J]. Chinese Pharmaceutical Journal, 2007, 42(14): 1098-1100
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参考文献
[1] CHEN J H，CHEN J. A study of feature of phenylpropanolamine absorption in intestine [J] . Chin J Hosp Pharm (中国医院药学杂志)，2000，20(2)：73-75.
[2] WAGNER D，SPAHN-LANGGNTH H，HANAFY A，et al. Intestinal drug effluxformulation and food effects [J] . Adv Drug Deliv Rev，2001，50(Suppl 1)：13-31.
[3] LIANG J，ZHOU A，CHEN M，et al. Negatively regulatory effects of paeoniflorin on immune cells [J] . Eur J Pharmacol，1990，189：901-902.
[4] OHTA H，MATSUMOTO K，SHIMIZU M，et al. Paeoniflorin attenuates learning impairment of aged rats on operant brightness discrimination task [J] . Pharmacol Biochem Be，1994，49(1)：213-217.
[5] WATANABE H. Candidates for cognitive enhancer extracted from medicinal plants，paeoniflorin and tetramethylpyrazine [J] . Behav Brain Res，1997，83(1-2)：135-141.
[6] YANG H O，KO W K，KIM J Y，et al. Paeoniflorin：an antihyperlipidemic agent from Paeonia lactiflora[J] . Fitoterapia，2004 ，75(1)：45-49.
[7] WILSON T H，WISEMAN G.The use of sacs of everted small intestine for the study of the transference of substances form the mucosal to the serosal surface [J] . J Physiol，1954，123：116.
[8] HE Y X，SUN J，CHENG G. Key role of the multidrug resistance P-glycoprotein in the intestinal absorption of drugs [J] . J Shenyang Pharm Univ(沈阳药科大学学报)，2004，21(5)：389-393.
[9] SU C Y. Role of P-glycoprotein in pharmacokinetics and its clinical implications [J] . Acta Pharm Sin(药学学报)，2005，40(8)：673-679.
[10] LU X S，LI Y. The joint altion of P-glycoprotein and cytochrome P450 3A in the drug absorption[J] .Foreign Med Sci Pharm (国外医学·药学分册)，2003，31(2)：108-111.
[11] ZHANG L，ZHENG Y，CHOW M S，et al. Investigation of intestinal absorption and disposition of green tea catechins by Caco-2 monolayer model [J] . Int J Pharm，2004，287(1-2)：1-12.
[12] NOBILIS M，HOLCAPEK M，KOLAROVA L，et al.Identification and determination of phase II nabumetone metabolites by high-performance liquid chromatography with photodiode array and mass spectrometric detection[J] . J Chromatogr A，2004，1031(1-2)：229-236.
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脚注
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基金
国家自然科学基金重大研究计划重点项目(90209005);国家重点基础研究发展计划(973计划)(2005CB523402)
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