单向灌流法研究丹参提取物中丹参素和原儿茶醛大鼠肠吸收特性  

Rat intestinal absorption trait of danshensu and protocatechuic aldehyde in Salviae Miltiorrhizae Radix et Rhizoma extract by single pass perfusion

作　　者：潘德城[1] 孙婷婷[1] 孙勇兵[2] 张国松[2] 饶小勇[2] 何双凤[2] 杨世林[2] 罗晓健[1,2] 

机构地区：[1]江西中医学院,江西南昌330006 [2]中药固体制剂制造技术国家工程研究中心,江西南昌330006

出　　处：《中草药》2011年第5期944-950,共7页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学基金资助项目(C0302050207);江西省教育厅高校科技项目(GJJ08324)

摘　　要：目的研究丹参提取物中丹参素和原儿茶醛的大鼠在体肠吸收动力学特征。方法采用大鼠在体肠单向灌流装置,并用质量法校正灌流液体积,考察灌流液体积流量、灌流液pH值、胆管结扎、丹参提取物质量浓度、吸收部位以及P-糖蛋白(P-gp)对丹参素和原儿茶醛吸收的影响,以HPLC法分别测定丹参素和原儿茶醛。结果在灌流体积流量0.2～0.8 mL/min,随着灌流体积流量的增大,丹参素和原儿茶醛的吸收速率常数(Ka)和表观吸收系数(Papp)均呈线性增大;在考察pH值为7.4、6.8、5.5时,供试液的pH值对丹参素和原儿茶醛的吸收有显著影响(P<0.05),丹参素和原儿茶醛的Ka和Papp均随pH值的降低而升高,pH 5.5和pH 6.8的吸收无显著差异,而pH 5.5与pH 7.4吸收有显著差异(P<0.05);胆管结扎组与不结扎组的丹参素和原儿茶醛的Ka和Papp均无显著差异;在不同吸收部位,丹参素的Ka和Papp分别按照十二指肠、空肠、回肠和结肠的顺序依次下降,原儿茶醛则下降趋势不明显,全肠段都有很好的吸收;在丹参提取物质量浓度0.8、1.5、2.2 mg/mL时小肠中丹参素的Ka和Papp随质量浓度升高而降低,而原儿茶醛吸收参数则无明显变化;含P-gp抑制剂组与不含P-gp抑制剂组相比,丹参素和原儿茶醛的Ka和Papp均无显著差异。结论灌流体积流量对丹参素和原儿茶醛的吸收有显著影响;随着pH值的降低,丹参素和原儿茶醛的吸收增加;胆管结扎与否对吸收没有显著影响;丹参素和原儿茶醛在整个肠段都有一定吸收,丹参素在肠上端吸收要比下端好;随着丹参提取物质量浓度的增大,原儿茶醛的Ka和Papp无明显变化,故其在肠道的吸收呈一级动力学过程,推测其吸收机制为被动扩散;而丹参素的Ka和Papp有明显减小的趋势,推测其吸收机制除被动扩散外,还可能有主动吸收或易化扩散;丹参素和原儿茶醛均不受P-gp的外排吸收影响。Objective To investigate the rat intestinal absorption kinetics of danshensu（DS） and protocatechuic aldehyde（PA） in Salviae Miltiorrhizae Radix et Rhizoma extract.Methods In situ single pass intestinal perfusion model was employed to investigate the effects of perfusion rate,perfusion solution pH value,bile duct ligation,drug concentrations,absorption sites and P-glycoprotein（P-gp） on absorption of DS and PA,and perfusion volume was corrected by gravimetric method.Meanwhile,the concentration of DS and PA in the perfusate were determined by HPLC.Results The drug absorption constant（Ka） and apparent absorption coefficient（Papp） of DS and PA increased linearly along with the increasing perfusion rates among the ranges of 0.2—0.8 mL/min.pH value of perfusion solution affected drug absorption（P 0.05）,Ka and Papp of DS and PA decreased with increasing pH value at pH values of 7.4,6.8,and 5.5.And at pH value of 5.5 and 6.8,the absorption had no significant difference,but there was significant difference at pH value between 5.5 and 7.4（P 0.05）.There was no significant difference in Ka and Papp value between bile duct ligation group and no ligation group.At different absorption sites,Ka and Papp of DS in the duodenum,jejunum,ileum,and colon sequence have a downward

关 键 词：丹参提取物 丹参素 原儿茶醛 单向灌流 吸收动力学 

分 类 号：R285.5[医药卫生—中药学] R286.02[医药卫生—中医学]