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双芪痛风胶囊对小鼠抗高尿酸血症及肾脏保护作用的分子机制研究

The molecular insight into the antihyperuricemic and renoprotective effect of Shuang Qi gout capsule in mice.

作者信息

Kodithuwakku Nandani Darshika, Feng Yi-dong, Zhang Yan-yan, Pan Min, Fang Wei-rong, Li Yun-man

机构信息

State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, PR China.

Technology Center of Shenzhen Neptunus Bioengineering Co., Ltd, Shenzhen 518057, PR China.

出版信息

J Ethnopharmacol. 2015 Apr 2;163:278-89. doi: 10.1016/j.jep.2015.01.013. Epub 2015 Jan 19.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Shuang-Qi gout capsule, a traditional Chinese medicine prescription, has been used in the treatment of, gout arthritis, arthralgia and inflammation. Since renal urate overload associated with severe disability including gout, elimination of excess renal uric acid is highly essential. Therefore, in this study we evaluated the antihyperuricemic and the renoprotective effect of the Shuang Qi gout capsule (SQ) with elucidation of its mechanism.

MATERIALS AND METHODS

We assessed the antihyperuricemic activity of SQ on urinary and serum uric acid, creatinine, blood urea nitrogen, fractional excretion of uric acid (FEUA) and glomerular filtration rate of creatinine and uric acid in potassium oxonate (PO) - induced mice as well as in non-induced mice. To illuminate the mechanism of antihyperuricemic activity, we investigated renal transport activity and the expression of mRNA levels in PO-induced and non-induced mice by western blot and RT-PCR methods.

RESULTS

SQ showed significant reduction in serum uric acid, creatinine and blood urea nitrogen levels and marked elevation of urine uric acid, creatinine and FEUA levels only in hyperuricemic mice. Furthermore, SQ could recover the altered expressions of proteins and mRNA levels of all the main renal transporters significantly in dose dependent manner.

CONCLUSIONS

SQ could effectively regulate the main renal transporters denoted its denote probable antihyperuricemic mechanism of SQ and its dose dependent uricosuric effect. In addition, SQ attenuated the deleterious effects of hyperuricemia with renal dysfunction. Thus SQ could be a potent antihyperuricemic agent which can perform as a safer and effective agent in the management of hyperuricemia via regulating the renal transporters.

摘要

民族药理学相关性

双岐痛风胶囊是一种中药方剂,已用于治疗痛风性关节炎、关节痛和炎症。由于与痛风等严重残疾相关的肾脏尿酸过载,消除多余的肾脏尿酸至关重要。因此,在本研究中,我们评估了双岐痛风胶囊(SQ)的降血尿酸和肾脏保护作用,并阐明其机制。

材料与方法

我们评估了SQ对草酸钾(PO)诱导的小鼠以及未诱导小鼠的尿尿酸、血清尿酸、肌酐、血尿素氮、尿酸排泄分数(FEUA)以及肌酐和尿酸的肾小球滤过率的降血尿酸活性。为了阐明降血尿酸活性的机制,我们通过蛋白质印迹和逆转录-聚合酶链反应方法研究了PO诱导和未诱导小鼠的肾脏转运活性和mRNA水平表达。

结果

仅在高尿酸血症小鼠中,SQ显著降低了血清尿酸、肌酐和血尿素氮水平,并显著提高了尿尿酸、肌酐和FEUA水平。此外,SQ能以剂量依赖的方式显著恢复所有主要肾脏转运蛋白的蛋白质和mRNA水平的改变表达。

结论

SQ可以有效调节主要的肾脏转运蛋白,这表明了SQ可能的降血尿酸机制及其剂量依赖性的促尿酸排泄作用。此外,SQ减轻了高尿酸血症对肾功能的有害影响。因此,SQ可能是一种有效的降血尿酸药物,通过调节肾脏转运蛋白,在高尿酸血症的管理中可作为一种更安全有效的药物。

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