车前子醇提物降低急性高尿酸血症小鼠血尿酸水平及机制研究

Research on Plantaginis Semen Extracts Reduce Level of Uric Acid in Hyperuricemia Mice and its Mechanism

摘要:

目的: 探讨车前子醇提物对高尿酸血症小鼠血清尿酸水平的影响及降尿酸作用机制。 方法: 车前子低、中、高剂量(1.17,2.34,4.68 g·kg^-1)和别嘌呤醇(10 mg·kg^-1)ig连续7 d,建立小鼠高尿酸血症模型,观测对氧嗪酸钾盐诱导的急性高尿酸血症小鼠血清尿酸与肌酐含量、肝脏黄嘌呤氧化酶(XOD)与腺苷脱氨酶(ADA)的活性、肾脏尿酸转运体(mURAT1) mRNA表达的影响。 结果: 与正常组比,模型组小鼠血清尿酸与肌酐含量和肝脏XOD与ADA活性显著增高,并上调肾脏尿酸转运体mURAT1 mRNA的表达。提取物低、中、高剂量组血清尿酸分别为(178.32±10.26),(148.77±13.59),(160.28±14.65) μmol·L^-1,明显低于模型组(235.65±19.38) μmol·L^-1(P<0.01)。血清肌酐分别为(56.12±4.58),(50.97±3.27),(52.45±4.66) μmol·L^-1,明显低于模型组(107.59±8.32) μmol·L^-1(P<0.01)。肝脏XOD活性分别为(23.18±3.72),(16.96±2.45),(14.62±3.43) U·g^-1,明显低于模型组(24.39±3.58) U·g^-1(P<0.05)。ADA活性分别为(4.70±0.44),(3.89±0.24),(4.08±0.58) U·mg^-1,明显低于模型组(5.92±0.84) U·mg^-1(P<0.05,P<0.01)。肾尿酸转运体mURAT1 mRNA的表达分别为1.83±0.12,1.52±0.13,1.72±0.11,明显低于模型组2.22±0.1(P<0.05,P<0.01)。 结论: 车前子醇提物能够降低高尿酸血症模型小鼠的血尿酸,改善高尿酸血症小鼠肾脏功能。抑制XOD与ADA活性并下调肾脏尿酸转运体mURAT1 mRNA的表达,是其降低高尿酸血症小鼠血清尿酸水平的可能机制。

Abstract:

Objective: To study the effect of Plantaginis Semen extracts (PASEs) on the level of uric acid in hyperuricemia mice and investigate the mechanism. Method: PASEs were administrated to hyperuricemia mice induced by potassium oxonate. The effects of PASEs on serum levels of uric acid, creatinine, and activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) in hyperuricemia mice were studied. Moreover, The effects of PASEs on renal urate transporter (mURAT1) were analyzed by semi-quantitative RT-PCR method. Result: Different dose groups of observing extract could obviously reduce the level of uric acid, inhibited hepatic xanthine oxidase and denosine deaminase activities in hyperuricemia mice. Furthermore, the PASEs could effectively down-regulate renal mURAT1 level in hyperuricemia mice. And it reversed oxonate-induced elevation in serum creatinine levels of mice. Conclusion: These findings suggested that the PASEs could obviously produce hypourice action by supressing hepatic XOD and ADA to reduce uric acid production and down-regulate renal mURAT1 to decrease urate reabsorption and enhance urate excretion in hyperuricemia mice.