【摘要】 目的研究9种黄酮类化合物和5种芪类化合物对血脑屏障上P-糖蛋白（P-gp）外排沙奎那韦的影响。方法以过表达P-gp的马丁达比犬肾上皮细胞（MDCKII-MDR1）作为血脑屏障体外模型。药物干预分为16组（n=4）,包括阴性对照组、阳性对照组、黄酮类实验I-IX组和芪类实验组Ⅰ-Ⅴ组。药物干预分别为50μmol·L^-1沙奎那韦（阴性对照组）;50μmol·L^-1沙奎那韦联用50μmol·L^-1维拉帕米（阳性对照组）;50μmol·L^-1沙奎那韦联用25μmol·L^-1黄酮类（黄酮类实验I-IX组）或联用25μmol·L^-1芪类化合物（芪类实验组Ⅰ-Ⅴ组）。药物干预时间均为4 h。用液相色谱质谱联用技术测定沙奎那韦在各组细胞内的积聚量。结果细胞内沙奎那韦积聚量:与阴性对照组（101.46±22.00）ng·mg^-1相比,柚皮素组（229.41±74.86）ng·mg^-1、桑黄素组（149.89±30.38）ng·mg^-1、白杨黄素组（209.75±65.35）ng·mg^-1、氧化白藜芦醇组（178.54±44.40）ng·mg^-1、染料木黄酮组（294.49±66.35）ng·mg^-1、表儿茶素组（212.27±49.70）ng·mg^-1、三乙酰白藜芦醇组（290.94±45.54）ng·mg^-1和白藜芦醇三甲醚组（205.55±35.16）ng·mg^-1,均显著升高,差异有统计学意义（P<0.05）;异槲皮苷组（61.98±11.02）ng·mg^-1、槲皮素组（41.54±4.92）ng·mg^-1和白藜芦醇组（29.59±4.61）ng·mg^-1细胞内沙奎那韦积聚量,均显著降低,差异有统计学意义（P<0.05）。结论一些黄酮类、芪类化合物可能对P-gp介导的沙奎那韦在血脑屏障上的转运过程产生调节作用。更多还原

【Abstract】 Objective To investigate the effects of 9 flavonoids and 5stilbenes on the P- glycoprotein（ P- gp） mediated efflux of saquinavir on blood- brain barrier（ BBB） in vitro. Methods Madin- Darby canine kidney cells（ MDCKII- MDR1） expressing P- gp were performed as an in vitro blood- brain barrier（ BBB） model. Incubations were divided into 16 groups（ n = 4）,including a negative control group,a positive control group,9 flavonoid intervention groups,and 5 stilbene intervention groups. In negative control group,cells were incubated in 50μmol·L^-1saquinavir. In positive control group,cells were incubated in50 μmol·L^-1saquinavir in the presence of 50 μmol · L^-1verapamil.In flavonoid intervention groups（ Ⅰ- Ⅸ）,cells were incubated in 50μmol·L^-1saquinavir in the presence of 25 μmol·L^-1certain flavonoid.In stilbene intervention groups（Ⅰ- Ⅴ）,cells were incubated in 50 μmol · L^-1saquinavir in the presence of 25μmol·L^-1certain stilbene. Incubations were terminated after 4 h. The intracellular concentrations of saquinavir were determined using a high- performance liquid chromatography- tandem mass spectrometry（ HPLC- MS / MS） method.Results Compared with the negative control group（ 101. 46 ± 22. 00） ng · mg^-1,the accumulation of saquinavir in MDCKII- MDR1 cells in the presence of naringenin（ 229. 41 ± 74. 86） ng · mg^-1,morinhydrate（ 149. 89 ± 30. 38）ng·mg^-1,chrysin（ 209. 75 ± 65. 35） ng · mg^-1,and oxyresveratrol（ 178. 54 ± 44. 40） ng · mg^-1,genistein（ 294. 49 ±66. 35） ng ·mg^-1,L- epicatechin（ 212. 27 ± 49. 70） ng ·mg^-1,triacetyl- resveratrol（ 290. 94 ± 45. 54）ng·mg^-1,and 3,4’,5- trimethoxy- trans- stilbene（ 205. 55 ±35. 16） ng·mg^-1increased significantly（ P < 0. 05）. In contrast,the accumulation of saquinavir in MDCKII- MDR1 cells in the presence ofisoquercitrin（ 61. 98 ± 11. 02）ng·mg^-1,quercetin（ 41. 54 ±4. 92） ng·mg^-1,and resveratrol（ 29. 59 ±4. 61） ng·mg^-1decreased significantly（ P <0. 05）.Conclusion Several flavonoids and stilbenes may exert modulaory effects on P- gp mediated efflux of saquinavir on BBB.更多还原