摘要
目的研究3,5,2’,4’-四羟基查尔酮(P40)对尿酸诱导的高尿酸血症小鼠尿酸排泄的影响,以及对尿酸肾脏转运体葡萄糖转运体9(GLUT9)、尿酸盐转运体1(URAT1)的调控作用。方法昆明种小鼠60只,随机分为正常组、模型组、P40 2.0、4.0、8.0 mg·kg-1组以及阳性对照组,分别灌胃给予受试药物5次;腹腔注射尿酸(150 mg·kg-1)诱导成高尿酸血症小鼠,磷钨酸法测定血尿酸水平和肝尿酸含量;RTPCR和Western blot检测小鼠肾脏GLUT9、URAT1的表达。结果 1 P40(4.0、8.0 mg·kg-1)剂量组明显降低高尿酸血症小鼠血清尿酸水平,与模型组相比,差异有统计学意义(P<0.05,0.01);各实验组肝尿酸含量降低,与正常组相比,差异有统计学意义(P<0.01)。2 P40各剂量组URAT1基因表达水平无明显变化,蛋白表达水平有下降趋势,但尚未达到统计学意义(P>0.05)。P40(2.0、4.0、8.0 mg·kg-1)组GLUT9基因表达水平具有下调趋势,但与模型组相比,差异无统计学意义(P>0.05);P40(4.0、8.0 mg·kg-1)组GLUT9蛋白表达水平明显下降,与模型组相比,差异有统计学意义。结论 P40具有促进高尿酸血症小鼠尿酸排泄的作用,其机制与下调GLUT9的蛋白表达有关。
Aim To investigate the effects of 3,5,2＇, 4＇ -tetrahydroxychalcone （P40） on urate excretion, as well as raRNA and protein expressions of renal URAT1 and GLUT9 in hyperuricemic mice. Methods Sixty Kunraing mice were randoraly divided into six groups： normal control group, hyperurieeraie group （model group）, P40 2.0, 4.0, 8.0 mg · kg-1 groups and positive control group. All drugs were administered in- tragastrically to mice for 5 doses. Hyperuriceraic mice were induced by intraperitoneal injection of uric acid （0.15 g · kg- 1 body weight） for 3 times. The urate levels were assayed with the phosphotungstic acid method. The raRNA and protein expressions of GLUT9 and URAT1 were determined by RT-PCR and Western blot. Results P40 at a dose of 4.0 and 8.0 mg ·kg-1 significantly reduced the serum urate levels in a dose-dependent manner, when compared with untreat- ed hyperuricemic mice （P 〈 0. 05 or 0. 01 ）. The he- patic urate contents decreased in untreated-and treated- hyperuricemic mice as compared with normal mice （P 〈 0. 01 ）. Furthermore, P40 had no influence on the renal URAT1 mRNA and protein expression levels, while it could down-regulate renal GLUT9 protein ex- pression but not mRNA expression in hyperuricemic mice. Conclusion P40 possesses potent uricosuric effects associated with urate reabsorption by down-regu- lating the protein expression of GLUT9 in kidney.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2015年第8期1091-1095,共5页
Chinese Pharmacological Bulletin
基金
国家自然科学基金资助项目(No 81260503
81360505)
云南省应用基础研究计划项目(No 2012FB020
2013FZ076
2013Z112)
