论文部分内容阅读
目的:观察复方黄甘颗粒对P-糖蛋白(P-gp)底物罗丹明123(R123)和非P-gp底物6-羧基荧光素(CF)经肠黏膜转运的影响,为复方黄甘颗粒与P-gp底物药物合理联用提供依据。方法:20只SPF级SD雄性大鼠,体重(250±20)g,用随机数字表法分为生理盐水组和复方黄甘颗粒组,每组10只。分别给予生理盐水20mL/kg和1.0g/L复方黄甘颗粒溶液20mL/kg灌胃,2次/d,连续7d。1周后大鼠禁食16～18h,用10%水合氯醛(3mL/kg)腹腔麻醉,取空肠标本3～4cm,用体外扩散池法检测2组大鼠空肠黏膜对R123和CF透过性的影响,比较2组吸收方向转运[黏膜侧(M)-浆膜侧(S)]和分泌方向转运(S-M)的表观渗透系数(Papp)及泵出比(ER)。结果:生理盐水组与复方黄甘组R123吸收方向的Papp分别为(3.54±0.86)×10-6和(2.39±0.44)×10-6cm/s,分泌方向的Papp分别为(8.68±3.76)×10-6和(8.34±2.47)×10-6cm/s;生理盐水组与复方黄甘组CF吸收方向的Papp分别为(5.40±3.20)×10-6cm/s和(3.28±1.41)×10-6cm/s,分泌方向的Papp分别为(5.09±1.71)×10-6cm/s和(3.98±1.02)×10-6cm/s;差异均无统计学意义(均P>0.05)。生理盐水组R123的ER为2.45,CF的ER为0.94;复方黄甘组R123的ER为3.50,CF的ER为1.21。结论:复方黄甘颗粒对肠黏膜P-gp的活性无明显影响,提示复方黄甘颗粒与R123类似的P-gp底物药物联合应用较为安全。
Objective: To observe the effects of compound Huanggan granule on intestinal mucosal transport of P-glycoprotein (P-gp) substrate Rh123 (R123) and non-P-gp substrate 6-carboxyfluorescein Gan particles and P-gp substrate drugs to provide a reasonable basis. Methods: Twenty SPF male Sprague Dawley rats weighing 250 ± 20 g were randomly divided into normal saline group and compound Huanggan granule group, with 10 rats in each group. Rats were given 20mL / kg normal saline and 1.0g / L compound Huang Gan granule solution 20mL / kg orally, 2 times / d, continuous 7d. After 1 week, rats were fasted for 16-18 h. Rats in jejunum were anesthetized with 10% chloral hydrate (3 mL / kg) The Papp and the pump-out ratio (ER) were compared between two groups in terms of transport direction [mucosal (M) -serum side (S)] and secretory transport (SM). Results: The Papp of R123 in saline group and compound Huanggan group were (3.54 ± 0.86) × 10-6 and (2.39 ± 0.44) × 10-6cm / s, respectively. Papp in secretion direction was (8.68 ± 3.76) (5.40 ± 3.20) × 10-6cm / s and (3.28 ± 1.41) × 10-6cm / s respectively in the normal saline group and compound Huanggan group Papp were (5.09 ± 1.71) × 10-6cm / s and (3.98 ± 1.02) × 10-6cm / s, respectively. There was no significant difference between the two groups (P> 0.05). The ER of R123 in saline group was 2.45 and the ER of CF was 0.94. The ER of R123 in compound Huanggan group was 3.50, and the ER of CF was 1.21. CONCLUSION: The compound Huang Gan granule has no obvious effect on the intestinal mucosal P-gp activity, suggesting that the compound Huang Gan granule and the R123 similar P-gp substrate drug combination safe.