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目的:研究川芎中阿魏酸和藁本内酯在不同肠段的吸收特征,探索指标成分单体和川芎提取物使用时的吸收变化,考察P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP)对这2个成分吸收的影响。方法:采用大鼠单向肠灌流模型,利用UHPLC测定灌流液中阿魏酸和藁本内酯的含量变化,分析二者在各肠段、川芎提取物不同质量浓度及含蛋白抑制剂情况下的含量变化情况,计算吸收速率参数(Ka)和有效渗透系数(Peff)。结果:阿魏酸与藁本内酯在肠道各段均有吸收,藁本内酯的吸收大于阿魏酸。阿魏酸在十二指肠的Ka=1.23×10~(-3)s~(-1),与空肠和回肠的吸收无显著性差异。阿魏酸在生药质量浓度12.5,20.0,40.0 g·L~(-1)下的吸收无显著性差异,但100.0 g·L~(-1)下的吸收较前3个质量浓度显著降低。阿魏酸在提取物中的吸收明显高于单体直接灌流,与川芎提取物组比较,丙磺舒组的阿魏酸吸收显著性增加。藁本内酯在十二指肠的Ka=3.58×10~(-3)s~(-1),肠道的吸收大小排序为回肠>十二指肠≈空肠>结肠,吸收随川芎提取物质量浓度的增加而降低。与川芎提取物组比较,藁本内酯在维拉帕米组和丙磺舒组的吸收均显著性增加,且丙磺舒组的吸收大于维拉帕米组。结论:阿魏酸吸收方式可能为促进扩散,存在载体参与,为MRP的底物。藁本内酯主要依靠载体的主动转运,可能是P-gp与MRP的底物,且受MRP影响更大。
OBJECTIVE: To study the absorption characteristics of ferulic acid and ligustilide in different segments of Ligusticum chuanxiong Hort, and to explore the absorption changes of the monomer components and the extract of Ligusticum chuanxiong Hort. To investigate the changes of P-glycoprotein (P-gp) and multidrug resistance Effect of drug-associated protein (MRP) on absorption of these two components. Methods: The rat model of unilateral intestinal perfusion was established. The contents of ferulic acid and ligustilide in the perfusate were determined by UHPLC. The intestinal mucosa and the ligustilide were separated by different concentrations of the extract of Rhizoma Ligustici and their inhibitors (Ka) and effective permeability coefficient (Peff) were calculated. Results: Ferulic acid and ligustilide were absorbed in all sections of the intestine, and ligustilide absorbed more than ferulic acid. Ferulic acid in the duodenum Ka = 1.23 × 10 -3 s -1, and the absorption of jejunum and ileum no significant difference. Ferulic acid had no significant difference in the concentrations of crude drug at the concentrations of 12.5, 20.0 and 40.0 g · L -1, but the absorption at 100.0 g · L -1 was significantly lower than that at the first three concentrations. Ferulic acid absorption in the extract was significantly higher than the monomer direct perfusion, and Chuanxiong extract group, probenecid group ferulic acid absorption increased significantly. The ligustilide’s Ka = 3.58 × 10 ~ (-3) s ~ (-1) in intestinal duodenum, the intestinal absorption size ranked ileum> duodenum ≈ jejunum> colon, Mass concentration increases and decreases. Compared with Rhizoma Chuanxiong Extract, the absorption of ligustilide in verapamil group and probenecid group increased significantly, and the absorption of probenecid group was greater than that of verapamil group. Conclusion: The ferulic acid absorption mode may be to promote the proliferation, there is carrier involved, as MRP substrate. The ligustilide mainly relies on the active transporter of the carrier, which may be the substrate of P-gp and MRP, and is more affected by MRP.