基于大鼠离体外翻肠囊模型研究不同粒径天麻粉的吸收特性

Study on Absorption Characteristics of Gastrodia elata Powder with Different Particle Sizes Based on Rat Everted Intestinal Sac Model in vitro

目的:比较不同粒径天麻粉中天麻素、巴利森苷A、巴利森苷B、巴利森苷C的肠吸收特征,探讨粒径对上述成分肠吸收的影响。方法:采用大鼠外翻肠囊模型,以累积吸收量(Q)和吸收速率常数(Ka)为指标,采用超高效液相色谱-串联质谱法测定不同剂量(2.5、5、10 g/L)和不同粒径(细粉146μm、极细粉52μm、超微粉37μm)的天麻粉中天麻素、巴利森苷A、巴利森苷B、巴利森苷C在不同肠段(十二指肠、空肠、回肠、结肠)中的吸收情况。结果:2.5 g/L天麻极细粉中天麻素和巴利森苷B的Q、Ka值(全肠段),巴利森苷C的Q值(结肠)和Ka值(回肠、结肠);2.5 g/L天麻超微粉中天麻素的Q、Ka值(全肠段),巴利森苷B的Q、Ka值(十二指肠、空肠、回肠),巴利森苷C的Ka值(结肠);5 g/L天麻极细粉中天麻素的Q值(十二指肠),巴利森苷A和巴利森苷B的Q值(全肠段),巴利森苷C的Q值(十二指肠、空肠);5 g/L天麻超微粉中天麻素的Q值(十二指肠、空肠、结肠)和Ka值(全肠段),巴利森苷B的Q值(十二指肠、回肠、结肠),巴利森苷C的Q值(十二指肠、回肠);10 g/L天麻极细粉中巴利森苷B的Q、Ka值(空肠、回肠),巴利森苷C的Q值(空肠、回肠)以及10 g/L天麻超微粉中天麻素的Q值(结肠)和Ka值(十二指肠),巴利森苷B的Q值(十二指肠、回肠、结肠)和Ka值(十二指肠、结肠),巴利森苷C的Q值(十二指肠、回肠)和Ka值(十二指肠)均较同剂量天麻细粉显著升高(P<0.05或P<0.01)。2.5 g/L天麻极细粉中巴利森苷A的Ka值(空肠),巴利森苷C的Q值(十二指肠);2.5 g/L天麻超微粉中巴利森苷A的Ka值(空肠、回肠),巴利森苷C的Q、Ka值(十二指肠、空肠);5 g/L天麻极细粉中天麻素的Ka值(空肠、回肠、结肠),巴利森苷A的Ka值(结肠),巴利森苷B的Ka值(回肠),巴利森苷C的Ka值(空肠、回肠);5 g/L天麻超微粉中天麻素和巴利森苷C的Ka值(空肠、回肠、结肠),巴利森苷A的Q值(空肠、结肠)和Ka值(结肠),巴利森苷B的Ka值(空肠、回肠);10 g/L天麻极细粉中巴利森苷A的Q、Ka值(回肠);10 g/L天麻超微粉中巴利森苷A的Q值(十二指肠)和Ka值(空肠),巴利森苷C的Ka值(空肠)均较同剂量天麻细粉显著降低(P<0.05或P<0.01)。2.5 g/L天麻细粉中天麻素的Q值(结肠),巴利森苷A的Q值(结肠)和Ka值(回肠、结肠),巴利森苷B的Q、Ka值(空肠、结肠),巴利森苷C的Q、Ka值(回肠、结肠);2.5 g/L天麻极细粉中天麻素的Q、Ka值(结肠),巴利森苷A的Q值(回肠、结肠)和Ka值(空肠、回肠、结肠),巴利森苷C的Ka值(结肠);2.5 g/L天麻超微粉中巴利森苷A和巴利森苷C的Q值(结肠)和Ka值(空肠、回肠、结肠),巴利森苷B的Q、Ka值(回肠、结肠);5 g/L天麻细粉中天麻素、巴利森苷A和巴利森苷C的Q、Ka值(结肠),巴利森苷B的Ka值(结肠);5 g/L天麻极细粉中天麻素和巴利森苷A的Q、Ka值(结肠),巴利森苷C的Q、Ka值(空肠、回肠、结肠);5 g/L天麻超微粉中天麻素的Q、Ka值(回肠、结肠),巴利森苷A的Q值(空肠、回肠、结肠),巴利森苷B的Q、Ka值(空肠、结肠),巴利森苷C的Q值(空肠、结肠)和Ka值(空肠、回肠、结肠);10 g/L天麻细粉中天麻素的Q值(结肠)以及巴利森苷A、巴利森苷B、巴利森苷C的Q、Ka值(空肠、回肠、结肠);10 g/L天麻极细粉中天麻素的Q值(结肠),巴利森苷A和巴利森苷C的Q、Ka值(空肠、回肠、结肠),巴利森苷B的Q、Ka值(结肠);10 g/L天麻超微粉中天麻素的Q值(结肠)和Ka值(空肠、回肠、结肠),巴利森苷A和巴利森苷C的Q、Ka值(空肠、回肠、结肠),巴利森苷B的Q值(空肠、回肠、结肠)和Ka值(回肠、结肠)均较同组十二指肠显著降低(P<0.05)。2.5 g/L天麻极细粉中天麻素的Q、Ka值(空肠),2.5 g/L天麻超微粉中天麻素的Q值(空肠、回肠)和Ka值(空肠),5 g/L天麻细粉中天麻素的Q、Ka值(空肠、回肠);2.5 g/L天麻极细粉中巴利森苷B的Q值(空肠、回肠)和Ka值(空肠),5 g/L天麻细粉中巴利森苷B的Ka值(空肠、回肠),10 g/L天麻极细粉中巴利森苷B的Ka值(回肠)均较同组十二指肠显著升高(P<0.05)。5 g/L以及10 g/L天麻细粉、极细粉、超微粉中天麻素、巴利森苷A、巴利森苷B、巴利森苷C的Q、Ka值(全肠段)均较同肠段同粒径2.5 g/L天麻粉显著升高(P<0.05或P<0.01)。结论:天麻中的4种有效成分在4个肠段均有吸收,且主要集中于小肠。天麻中的天麻素可能为被动吸收,巴利森苷类则可能为主动转运;粒径可影响上述4种有效成分的肠吸收特性。

OBJECTIVE:To compare the absorption characteristics of gastrodin,parishin A,parishin B and parishin C of Gastrodia elata powder,and to explore the effect of particle size on intestinal absorption of above components.METHODS:Based on everted intestinal sac model,using accumulative absorption amount(Q)and absorption rate constant(Ka)as indexes,UPLC-MS/MS method was used to determine the absorption of gastrodin,parishin A,parishin B and parishin C from different doses(2.5,5,10 g/L)of G.elata powder with different particle sizes(fine powder 146μm,superfine powder 52μm,ultrafine powder 37μm)in different segments(duodenum,jejunum,ileum and colon).RESULTS:Q and Ka of gastrodin and parishin B(intestinal segment),Q(colon)and Ka(ileum and colon)of parishin C in 2.5 g/L G.elata superfine powder;Q and Ka of gastrodin(intestinal segment),Q and Ka of parishin B(duodenum,jejunum,ileum)and Ka of parishin C(colon)in 2.5 g/L G.elata ultrafine powder;Q of gastrodin(duodenum),Q of parishin A and parishin B(intestinal segment)and Q of parishin C(duodenum,jejunum)in 5 g/L G.elata superfine powder;Q(duodenum jejunum,colon)and Ka(intestinal segment)of gastrodin,Q of parishin B(duodenum,ileum and colon)and Q of parishin C(duodenum,ileum)in 5 g/L G.elata ultrafine powder;Q and Ka of parishin B(jejunum,ileum),Q of parishin C(jejunum,ileum)in 10 g/L G.elata superfine powder as well as Q(colon)and Ka(duodenum)of gastrodin,Q(duodenum,ileum,colon)and Ka(duodenum,colon)of parishin B,Q(duodenum,ileum)and Ka(duodenum)of parishin C in 10 g/L G.elata ultrafine powder were all increased significantly,compared with the same dose of G.elata fine powder(P<0.05 or P<0.01).Ka of parishin A(jejunum)and Q of parishin C(duodenum)in 2.5 g/L G.elata superfine powder;Ka of parishin A(jejunum,ileum),Q and Ka of parishin C(duodenum,jejunum)in 2.5 g/L G.elata ultrafine powder;Ka of gastrodin(jejunum,ileum and colon),Ka of parishin A(colon),Ka of parishin B(ileum)and Ka of parishin C(jejunum,ileum)in 5 g/L G.elata superfine powder;Ka of gastrodin and parishin C(jejunum,ileum and colon),Q(jejunum,colon)and Ka(colon)of parishin A,Ka of parishin B(jejunum,ileum)in 5 g/L G.elata ultrafine powder;Q and Ka of parishin A(ileum)in 10 g/L G.elata superfine powder;Q(duodenum)and Ka(jejunum)of parishin A,Ka of parishin C(jejunum)in 10 g/L G.elata ultrafine powder were decreased significantly,compared with the same dose of G.elata fine powder(P<0.05 or P<0.01).Q of gastrodin(colon),Q(colon)and Ka(ileum,colon)of parishin A,Q and Ka of parishin B(jejunum,colon),Q and Ka of parishin C(ileum,colon)in 2.5 g/L G.elata fine powder;Q and Ka of gastrodin(colon),Q(ileum,colon)and Ka(jejunum,ileum,colon)of parishin A,Ka of parishin C(colon)in 2.5 g/L G.elata superfine powder;Q(colon)and Ka(jejunum,ileum,colon)of parishin A and C,Q and Ka(ileum,colon)of parishin B in 2.5 g/L G.elata ultrafine powder;Q and Ka of gastrodin,parishin A and C(colon),Ka of parishin B(colon)in 5 g/L G.elata fine powder;Q and Ka of gastrodin and parishin A(colon),Q and Ka of parishin C(jejunum,ileum,colon)in 5 g/L G.elata superfine powder;Q and Ka of gastrodin(ileum,colon),Q of parishin A(jejunum,ileum,colon),Q and Ka of parishin B(jejunum,colon),Q(jejunum,colon)and Ka(jejunum,ileum,colon)of parishin C in 5 g/L G.elata ultrafine powder;Q of gastrodin(colon),Q and Ka of parishin A,B and C(jejunum,ileum,colon)in 10 g/L G.elata fine powder;Q of gastrodin(colon),Q and Ka of parishin A and C(jejunum,ileum,colon),Q and Ka of parishin B(colon)in 10 g/L G.elata superfine powder;Q(colon)and Ka(jejunum,ileum,colon)of gastrodin,Q and Ka of parishin A and C(jejunum,ileum,colon),Q(jejunum,ileum,colon)and Ka(ileum,colon)of parishin B in 10 g/L G.elata ultrafine powder were decreased significantly,compared with duodeum of the same group(P<0.05).Q and Ka of gastrodin(jejunum)in 2.5 g/L G.elata superfine powder,Q(jejunum,ileum)and Ka(jejunum)of gastrodin in 2.5 g/L G.elata ultrafine powder,Q and Ka of gastrodin(jejunum,ileum)in 5 g/L G.elata fine powder;Q(jejunum,ileum)and Ka(jejunum)of parishin B in 2.5 g/L G.elata superfine powder,Ka of parishin B(jejunum,ileum)in 5 g/L G.elata superfine powder,Ka of parishin B(ileum)in 10 g/L G.elata superfine powder were increased significantly,compared with duodenum of the same group(P<0.05).Q and Ka of gastrodin,parishin A,B and C(intestinal segment)in 5 and 10 g/L G.elata fine,superfine and ultrafine powder were increased significantly,compared with 2.5 g/L G.elata powder with same particle size in same intestinal segment(P<0.05 or P<0.01).CONCLUSIONS:The four active components of G.elata are absorbed in four intestinal segments and mainly concentrate in the small intestine.The gastrodin of G.elata may be absorbed passively,while the balisensides may be transported actively.The particle size can affect the intestinal absorption characteristics of the four active components.