绵萆薢水提物及其主要成分薯蓣皂苷对肾小管上皮细胞膜乳腺癌耐药蛋白Bcrp的调控  

Effect of Rhizoma Dioscoreae Septemlobae extracts and Dioscin on the breast cancer resistance protein distributed in renal tubular epithelial cells

作　　者：王晓华[1] 周燕[1] 王沛 苏筠霞[3] 魏玉辉[1] 

机构地区：[1]兰州大学第一医院药剂科,甘肃兰州730000 [2]兰州大学第二临床医学院,甘肃兰州730030 [3]兰州大学第一医院肾病科,甘肃兰州730000

出　　处：《兰州大学学报（医学版）》2017年第6期35-40,共6页Journal of Lanzhou University（Medical Sciences）

基　　金：兰州大学中央高校基本科研项目(lzujbky-2012-164)

摘　　要：目的探讨绵萆薢水提物及其主要成分薯蓣皂苷对分布于大鼠肾小管上皮细胞膜的乳腺癌耐药蛋白(Bcrp/Abcg2)的调控。方法雄性Wistar大鼠随机分为正常组、模型对照组、模型组、别嘌醇组(2.5 mg/kg)、绵萆薢水提物和薯蓣皂苷高、中、低剂量(638.43、319.22、159.61 mg/(kg·d))组(n=8)。用氧嗪酸钾联合乙胺丁醇制备高尿酸血症大鼠模型,从造模第1天起连续灌胃给予生理盐水和不同剂量的绵萆薢水提物或薯蓣皂苷,1次/天,至给药第10天,采用HPLC测定血尿酸及尿酸排泄量,并通过Western Blot检测Bcrp蛋白表达水平,采用离体肾灌流实验,考察Bcrp抑制剂新生霉素对大鼠累积尿酸排泄量的影响。结果模型组大鼠血尿酸水平显著升高,尿尿酸排泄减少,其肾脏组织中Bcrp的蛋白表达水平均显著降低,高剂量绵萆薢水提物及薯蓣皂苷可显著降低高尿酸血症大鼠的血清尿酸水平,增加尿尿酸排泄量,并增加肾脏组织中Bcrp蛋白表达水平。此外,抑制Bcrp可显著降低尿尿酸排泄量。结论绵萆薢水提物及高剂量薯蓣皂苷可增加Bcrp的表达,这可能是其抗高尿酸血症的一个重要机制。Objective To investigate the effect of Rhizoma Dioscoreae Septemlobae extracts and dioscin on the breast cancer resistance protein distributed in renal tubular epithelial cells in rats. Methods Wistar rats were randomly divided into 10 groups： normal group, control group, model group, allopurinol group （2.5 mg/ kg）, high/middle/low groups treated with Rhizoma Dioscoreae Septemlobae extracts or dioscin （638.43, 319.22, 159.61 mg/（kg ~ d））. Experimental animal model of hyperuricemia was induced by uricase inhibitor potassium oxonate with ethambutol. Except for the normal group, others were administered by gavage oncedaily with potassium oxonate （250 mg/kg） with ethambutol （250 mg/kg） or water （vehicle） for seven consecu- tive days to induce hyperuricemia. Allopurinol and Rhizorna Dioscoreae Septemlobae extracts or dioscin of different doses were orally initiated from day 1 to 10. After treatment, uric acid in serum and its cumulative renal excretion amount were determined by HPLC, respectively. The protein of breast cancer resistance pro- tein （Bcrp） in the mice kidney was analyzed by Western blot. In addition, the effect of Bcrp inhibitor to the cu- mulative renal excretion amount of uric acid was investigated by renal perfusion technology. Results Serum levels of uric acid could be increased by potassium oxonate with ethambutol significantly as compared with that of the control mice. After treatment of Rhizoma Dioscoreae Septemlobae extracts in high dose or dioscin, uric acid levels in serum were decreased when compared with those before treatment, and a higher Bcrp expression was observed. Furthermore, the cumulative renal excretion of uric acid could be inhibited by Bcrp inhibitor. Conclusion Rhizoma Dioscoreae Septemlobae extracts or dioscin could increase the expression of Bcrp, which could be one of the important mechanisms of their anti-hyperuricemic function.

关 键 词：绵萆薜水提物 薯蓣皂苷 乳腺癌耐药蛋白 高尿酸血症 

分 类 号：R9[医药卫生—药学]