CAJ | 학술논문

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、P402.0、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；RT-PCR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。
목적연구3,5,2’,4’-사간기사이동(P40)대뇨산유도적고뇨산혈증소서뇨산배설적영향,이급대뇨산신장전운체포도당전운체9(GLUT9)、뇨산염전운체1(URAT1)적조공작용。방법곤명충소서60지,수궤분위정상조、모형조、P402.0、4.0、8.0 mg·kg-1조이급양성대조조,분별관위급여수시약물5차；복강주사뇨산(150 mg·kg-1)유도성고뇨산혈증소서,린오산법측정혈뇨산수평화간뇨산함량；RT-PCR화Western blot 검측소서신장GLUT9、URAT1적표체。결과① P40(4．0、8．0 mg·kg-1)제량조명현강저고뇨산혈증소서혈청뇨산수평,여모형조상비,차이유통계학의의(P<0．05,0．01)；각실험조간뇨산함량강저,여정상조상비,차이유통계학의의(P<0．01)。② P40각제량조URAT1기인표체수평무명현변화,단백표체수평유하강추세,단상미체도통계학의의( P >0．05)。 P40(2．0、4．0、8．0 mg · kg-1)조GLUT9기인표체수평구유하조추세,단여모형조상비,차이무통계학의의(P>0．05)；P40(4．0、8．0 mg·kg-1)조GLUT9단백표체수평명현하강,여모형조상비,차이유통계학의의。결론 P40구유촉진고뇨산혈증소서뇨산배설적작용,기궤제여하조GLUT9적단백표체유관。
Aim To investigate the effects of 3 ,5 ,2 ’ , 4’-tetrahydroxychalcone (P40) on urate excretion, as well as mRNA and protein expressions of renal URAT1 and GLUT9 in hyperuricemic mice. Methods Sixty Kunming mice were randomly divided into six groups:normal control group, hyperuricemic 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. Hyperuricemic 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 mRNA 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.