摘要
目的:通过检测黄芪多糖(APS)对P-糖蛋白(P-gp)底物罗丹明123(Rh123)在大鼠体内口服吸收的影响,验证APS是否对大鼠肠道上皮细胞P-gp功能有抑制作用。方法:采用水提醇沉法制备APS,并采用苯酚硫酸法和BCA蛋白定量试剂盒分别检测黄芪中APS及蛋白质的含量。体内实验选用30只SD大鼠作为受试对象,以纯化水为空白对照,维拉帕米(0.01 mg/g)为阳性对照,并设置不同给药时长(2 d,5 d,10 d)的APS给药组(0.1 mg/g),每组6只。各给药组每日以1 ml/100 g的给药体积灌胃给药1次,并于末次给药30 min后每只大鼠灌胃0.005 mg/g Rh1231 ml/100 g,采用荧光酶标法测定给药后15 min,30 min,60 min,90 min,120 min,180 min,240 min,360 min后各组大鼠血浆中Rh123血药浓度变化,并使用Phoenix WinNonlin软件拟合吸收相关的药代动力学参数。结果:样品中APS含量为(54.09±1.69)%,蛋白质含量为(8.89±0.30)%。与空白组比较,APS-2 d组大鼠AUC_(0-t)明显增加,APS-5 d组和维拉帕米组大鼠AUC_(0-t)及C_(max)均明显增加,差异均有统计学意义(P<0.01),而APS-10 d组大鼠的药代动力学参数与空白组比较,差异均无统计学意义(P>0.05)。APS-2 d组、APS-5 d组大鼠C_(max)和AUC_(0-t)与维拉帕米组比较,差异均无统计学意义(P>0.05);APS-10 d组大鼠C_(max)和AUC_(0-t)明显低于维拉帕米组,差异有统计学意义(P<0.01)。结论:APS可促进大鼠Rh123口服吸收,表明其对大鼠肠道上皮细胞P-gp功能具有抑制作用,给药时长为5 d时作用最明显。
Objective:To validate whether astragalus polysaccharides(APS)inhibit P-glycoprotein(P-gp)function in rat intestinal epithelium by evaluating their effects on oral absorption of Rhodamine 123(Rh123),a prototypical P-gp substrate.Methods:APS was extracted via water extraction-alcohol precipitation.APS and protein content in Huangqi were quantified using phenol-sulfuric acid method and BCA protein assay kit,respectively.Thirty SD rats were divided into:blank control(purified water),positive control(0.01 mg/g verapamil),and APS groups(0.1 mg/g)with different administration durations(2 d,5 d,10 d;n=6/group).Each administration group received intragastic administration once daily at a dosage of 1 mg/100 g.Thirty minutes after the last administration,rats were orally administered Rh123(0.005 mg/g,1 ml/100 g).Plasma Rh123 concentrations were measured via fluorescence microplate reader at 15,30,60,90,120,180,240,and 360 min post-dosing.Pharmacokinetic parameters were calculated using Phoenix WinNonlin software.Results:APS content was 54.09%±1.69%and protein content 8.89%±0.30%.Compared with the blank group:APS-2 d group showed significantly increased AUC_(0-t)(P<0.01);APS-5 d and verapamil groups exhibited significantly increased AUC_(0-t)and C_(max)(P<0.01);APS-10 d group showed no significant pharmacokinetic differences(P>0.05).No significant differences in C_(max) or AUC_(0-t) were observed between APS-2 d/5 d and verapamil groups(P>0.05),while APS-10 d showed significantly lower values than verapamil(P<0.01).Conclusion:APS enhances oral absorption of Rh123 in rats,indicating P-gp inhibition in intestinal epithelial cells,with maximal effect at 5-day administration.
作者
余晓夏
蒋畅
雷婷
陈念
张捷
韩静
Yu Xiaoxia;Jiang Chang;Lei Ting;Chen Nian;Zhang Jie;Han Jing(College of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou Fujian 350122;Fujian Academy of Chinese Medical Sciences,Fuzhou Fujian 350003)
出处
《山西中医药大学学报》
2025年第8期855-860,共6页
Journal of Shanxi University of Chinese Medicine
基金
福建省属公益类科研院所基本科研专项项目(2024R1003009)。
关键词
黄芪多糖
P-糖蛋白
罗丹明123
药代动力学
astragalus polysaccharides
P-glycoprotein
Rhodamine 123
pharmacokinetics
