目的考察丹参素冰片酯(DBE)及丹参素钠-冰片(SDSS-B)等摩尔联合用药的脑部靶向作用与其对P-糖蛋白表达的影响。方法采用LC-MS分析大鼠尾静脉注射DBE、SDSS-B及SDSS后脑部丹参素分布量;蛋白免疫印迹法分析3种给药方式对大鼠脑组织P-糖蛋白(P-gp)表达量的影响。结果以大鼠脑部丹参素分布定性评价其脑靶向大小为:DBE(SDSS-B)〉SDSS;蛋白免疫印迹结果分析显示:DBE和SDSS-B给药均可有效降低大鼠海马组织P-gp表达水平(P〈0.01,与Control组对比;P〈0.01,与SDSS组对比),其表达量在给药45 min时分别降至(47.58±2.28)%及(46.54±1.41)%;SDSS给药对P-gp表达量几乎无明显抑制作用(P〉0.05在5、15、45、60 min,与Control组对比)。结论 DBE和SDSS-B均表现出脑部靶向作用,其靶向作用与其降低脑组织P-gp表达量有关。
Aim To investigate the relationship between the brain targeting effect and P-glycoprotein( Pgp) expression level of Danshensu borneol ester( DBE)and the combination use of sodium Danshensu and borneol( SDSS-B). Methods The liquid chromatography mass spectrometry( LC-MS) method was applied to investigate the accumulation of Danshensu( DSS) in rat brain tissues after intravenous injection of DBE,SDSS-B and SDSS. Also their effect on regulating the expression level of P-gp in rat hippocampus was investigated using Western blot. Results The brain targeting effect of DBE,SDSS-B was qualitatively analyzed through the brain distribution of DSS,and the result was DBE( SDSS-B) SDSS( P〈0. 01). Meanwhile,the brain distribution of DBE group was slightly lower than SDSS-B group at 15 min,while at 30 min DBE washigher than that of SDSS-B. DBE demonstrated a better slow release property compared to SDSS-B. Western blot analysis indicated that DBE,SDSS-B were more effective in inhibiting the expression of P-gp than SDSS in rat hippocampus( P〈0. 01 vs control or SDSS group),and the lowest P-gp expression was obtained with( 47. 58 ± 2. 28) % and( 46. 54 ± 1. 41) % at 45 min after administration of DBE or SDSS-B. Once the administration time was extended to 60 min,the inhibitory effect on P-gp expression of DBE was stronger thanSDSS-B[( 85. 04 ± 1. 42) % vs( 95. 29 ± 0. 98) %].However,no significant inhibition of P-gp expression in rat hippocampus was found throughout the treatment of SDSS( P〈0. 05 at 5,15,45,60 min,vs control group). Conclusion An attenuated expression level of P-gp can be realized by DBE and SDSS-B,which is advantageous to their brain targeting.