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三妙丸作为降血尿酸药物的双重作用:下调高尿酸血症小鼠肝脏 XOD 和肾脏 mURAT1。

The dual actions of Sanmiao wan as a hypouricemic agent: down-regulation of hepatic XOD and renal mURAT1 in hyperuricemic mice.

机构信息

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Han kou Road 22, Nanjing 210093, PR China.

出版信息

J Ethnopharmacol. 2010 Mar 2;128(1):107-15. doi: 10.1016/j.jep.2009.12.035. Epub 2010 Jan 4.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Sanmiao wan (SMW) is widely used for the treatment of gout and hyperuricemia in traditional Chinese medicine.

AIM OF THE STUDY

The aim of the present study was to investigate the hypouricemic effects of SMW and its possible mechanism in potassium oxonate-induced hyperuricemic mice.

MATERIALS AND METHODS

SMW at 489, 978 and 1956 mg/kg was orally administered to hyperuricemic and normal mice, and standard drug allopurinol (2.5mg/kg) was served as a positive control. The effects of SMW on serum, urine and liver levels of uric acid, serum levels of creatinine, and activity of hepatic xanthine oxidase (XOD) were measured in mice. Moreover, the effects of SMW on the mRNA and protein levels of hepatic XOD and renal urate transporter 1 (mURAT1) in mice were analyzed by semi-quantitative RT-PCR and Western blotting methods, respectively.

RESULTS

SMW significantly reduced uric acid levels in serum and liver, inhibited hepatic XOD activity, mRNA and protein levels in hyperuricemic mice. Furthermore, SMW could effectively down-regulate renal mURAT1 mRNA and protein levels of hyperuricemic mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. However, SMW did not show any effects in normal mice.

CONCLUSION

These findings suggested that SMW produced dual hypouricemic actions by suppressing hepatic XOD to reduce uric acid production and down-regulating renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemic mice.

摘要

民族药理学相关性

三妙丸(SMW)在中医中广泛用于治疗痛风和高尿酸血症。

研究目的

本研究旨在探讨 SMW 对氧嗪酸钾诱导的高尿酸血症小鼠的降尿酸作用及其可能机制。

材料和方法

将 SMW 以 489、978 和 1956mg/kg 的剂量口服给予高尿酸血症和正常小鼠,以标准药物别嘌醇(2.5mg/kg)作为阳性对照。测量 SMW 对小鼠血清、尿液和肝脏尿酸水平、血清肌酐水平以及肝脏黄嘌呤氧化酶(XOD)活性的影响。此外,通过半定量 RT-PCR 和 Western blotting 方法分析 SMW 对小鼠肝脏 XOD 和肾脏尿酸转运蛋白 1(mURAT1)的 mRNA 和蛋白水平的影响。

结果

SMW 显著降低了高尿酸血症小鼠的血清和肝脏尿酸水平,抑制了肝脏 XOD 活性、mRNA 和蛋白水平。此外,SMW 可有效下调高尿酸血症小鼠的肾脏 mURAT1 mRNA 和蛋白水平。并逆转了氧嗪酸钾诱导的小鼠血清肌酐水平升高。然而,SMW 在正常小鼠中没有表现出任何作用。

结论

这些发现表明,SMW 通过抑制肝脏 XOD 减少尿酸生成和下调肾脏 mURAT1 减少尿酸重吸收并增强尿酸排泄,对高尿酸血症小鼠产生双重降尿酸作用。

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