State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Chin J Nat Med. 2013 May;11(3):214-21. doi: 10.1016/S1875-5364(13)60019-9.
The present study was undertaken to characterize the effects of Wuling San on urate excretion and renal function, and explore its possible mechanisms of action in hyperuricemic mice.
Mice were administered with 250 mg·kg(-1) potassium oxonate by gavage once daily (10 animals/group) for seven consecutive days to develop a hyperuricemia model. Different doses of Wuling powder were orally initiated on the day 1 h after oxonate was given, separately. Allopurinol was used as a positive control. Serum and urine levels of uric acid and creatinine, and fractional excretion of uric acid (FEUA) were measured in hyperuricemic mice treated with Wuling San and allopurinol. Simultaneously, renal mRNA and protein levels of urate transporter 1 (mURAT1), glucose transporter 9 (mGLUT9), organic anion transporter 1 (mOAT1), as well as organic cation/carnitine transporters mOCT1, mOCT2 and mOCTN2, were assayed by semi-quantitative RT-PCR and Western blot methods, respectively.
Compared to the hyperuricemia control group, Wuling San significantly reduced serum uric acid and creatinine levels, increased 24 h urate and creatinine excretion, and FEUA in hyperuricemic mice, exhibiting its ability to enhance urate excretion and improve kidney function. Wuling San was found to down-regulate mRNA and protein levels of mURAT1 and mGLUT9, as well as up-regulate mOAT1 in the kidney of hyperuricemic mice. Moreover, Wuling San up-regulated renal mRNA and protein levels of mOCT1, mOCT2 and mOCTN2, leading to kidney protection in this model.
本研究旨在探讨五苓散对尿酸排泄和肾功能的影响,并探讨其在高尿酸血症小鼠中的作用机制。
通过灌胃给予 250 mg·kg(-1) 氧嗪酸钾,每天 1 次,连续 7 天,建立高尿酸血症小鼠模型。在给予氧嗪酸钾后 1 h 开始给予不同剂量的五苓散粉末,分别进行口服治疗。别嘌醇作为阳性对照。测定高尿酸血症小鼠用五苓散和别嘌醇治疗后血清和尿液尿酸和肌酐水平及尿酸排泄分数(FEUA)。同时,采用半定量 RT-PCR 和 Western blot 方法检测尿酸转运体 1(mURAT1)、葡萄糖转运蛋白 9(mGLUT9)、有机阴离子转运体 1(mOAT1)以及有机阳离子/肉碱转运体 mOCT1、mOCT2 和 mOCTN2 的肾脏 mRNA 和蛋白水平。
与高尿酸血症对照组相比,五苓散可显著降低高尿酸血症小鼠血清尿酸和肌酐水平,增加 24 h 尿酸和肌酐排泄,FEUA 升高,表明其具有增强尿酸排泄和改善肾功能的作用。五苓散可下调高尿酸血症小鼠肾脏 mURAT1 和 mGLUT9 的 mRNA 和蛋白水平,并上调 mOAT1。此外,五苓散上调了肾脏 mOCT1、mOCT2 和 mOCTN2 的 mRNA 和蛋白水平,从而对该模型起到了肾脏保护作用。