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从细胞水平和动物水平考察冰片对葛根素和梓醇口服吸收及穿透血脑屏障入脑的影响,筛选适合梓葛复方口服制剂的冰片浓度。采用原代大鼠脑微血管内皮细胞和星型胶质细胞共培养建立体外血脑屏障模型,利用此模型研究6.25~100mg·L~(-1)冰片对葛根素、梓醇转运的影响。小鼠分别灌胃给予0,25,50,100 mg·kg~(-1)冰片溶液后再立即灌胃给予葛根素(200mg·kg~(-1))、梓醇(45 mg·kg-1)纳米晶混悬液,比较葛根素、梓醇在血浆和脑组织中的药动学参数。脑微血管内皮细胞和星型胶质细胞共培养7 d后,屏障功能基本形成。与未加入冰片组相比,冰片质量浓度为12.5~100 mg·L~(-1)时,葛根素、梓醇跨血脑屏障模型的渗透系数显著增大(P<0.05),冰片作用于共培养模型2 h后的跨内皮细胞电阻值极显著降低(P<0.01)。小鼠灌胃50 mg·kg-1和100 mg·kg~(-1)冰片能显著促进葛根素的口服吸收,但冰片对梓醇的口服吸收无显著影响。100 mg·kg~(-1)冰片组葛根素的AUC脑/AUC血显著高于其余3组(P<0.05),梓醇则是50 mg·kg~(-1)组最高(P<0.05)。就脑组织AUC而言,葛根素以100 mg·kg~(-1)组最大,显著高于其余各组(P<0.05);梓醇以50 mg·kg~(-1)组最大,但与100 mg·kg~(-1)组无显著性差异。可见,冰片能促进葛根素、梓醇口服给药的入脑量,质量浓度以100 mg·kg~(-1)为佳。
The effects of borneol on oral absorption of puerarin and catalpol and penetration into the brain through the blood-brain barrier were investigated at cellular and animal levels, and the concentrations of borneol suitable for Ziege compound oral preparation were screened. The in vitro BBB model was established by co-culture of primary rat brain microvascular endothelial cells and astrocytes. The model was used to study the effects of borneol (6.25-100 mg · L -1) on the transport of puerarin and catalpol. The mice were orally administered with 0, 25, 50, 100 mg · kg -1 borneol solution and then intragastrically given puerarin (200 mg · kg -1) and catalpol (45 mg · kg -1) Nanocrystalline suspension, compared puerarin, catalpol in plasma and brain pharmacokinetic parameters. After co-cultured with cerebral microvascular endothelial cells and astrocytes for 7 days, barrier function basically formed. Compared with no borneol group, the permeation coefficient of puerarin and catalpol in the blood-brain barrier model increased significantly (P <0.05) when borneol concentration was 12.5-100 mg · L -1, After 2 h of co-culture, the trans-endothelial cell resistance decreased significantly (P <0.01). Oral administration of 50 mg · kg -1 and 100 mg · kg -1 of borneol could significantly promote the oral absorption of puerarin in mice, but borneol had no significant effect on the oral absorption of catalpol. The AUC brain / AUC blood of puerarin in 100 mg · kg -1 borneol group was significantly higher than that in the other 3 groups (P <0.05), and catalpol was the highest in 50 mg · kg -1 group ). In terms of AUC of brain tissue, puerarin was the highest in 100 mg · kg -1 group and significantly higher than the other groups (P <0.05). Catalpol was the largest in 50 mg · kg -1 group There was no significant difference with 100 mg · kg -1 group. Can be seen, borneol can promote puerarin, catalpol oral administration of brain volume, mass concentration of 100 mg · kg ~ (-1) is better.