藏药长花铁线莲及其主要成分calcoside D降低急性高尿酸血症小鼠尿酸水平及作用机制研究

目的探讨长花铁线莲醇提物对急性高尿酸血症小鼠尿酸水平的影响及其主要成分降尿酸的作用机制。方法将70只昆明小鼠按体质量均衡随机分为空白组,急性高尿酸血症模型组,别嘌呤醇组(10 mg·kg^-1),长花铁线莲总提物高、低剂量组(2.34、1.17 g·kg^-1),calcoside D高、低剂量组(50、20 mg·kg^-1),每组10只,连续灌胃7 d,末次给药前30 min注射350 mg·kg^-1氧嗪酸钾造急性高尿酸血症模型。检测各组血清尿酸(UA)、肝脏黄嘌呤氧化酶(XOD)、肿瘤坏死因子(TNF-α)、白介素-1β(IL-1β)、尿素氮(BUN)含量及肝脏XOD、腺苷脱氨酶(ADA)活力,RT-PCR测定肾脏转运体mURAT1、mOAT1、mGLUT9 mRNA相对表达量。结果与模型组相比,长花铁线莲醇提物高、低剂量组和calcoside D高、低剂量组均能显著降低血清UA值与抑制肝脏XOD活力(P <0.05),calcoside D高、低剂量组能显著降低血清中BUN、IL-1β(P <0.05),calcoside D高剂量组能显著降低TNF-α的含量(P <0.05),calcoside D高、低剂量组均能抑制肝脏ADA活力(P <0.01),下调肾脏mURAT1(P <0.01)、上调mOAT1 mRNA(P <0.001)的表达,calcoside D低剂量组能显著下调mGLUT9 mRNA的表达(P <0.001)。结论长花铁线莲与calcoside D均具有显著降尿酸的作用,且calcosideD具有一定的肾脏保护作用和抗炎作用,抑制XOD与ADA活力及下调肾脏mURAT1、mGLUT9 mRNA的表达,上调mOAT1 mRNA的表达为calcoside D降尿酸的可能机制。

Reducing Uric Acid Level of Acute Hyperuricemia Model Mice by Clematis rehderiana Craib and Its Main Components

Objective To investigate the effect of ethanol extract of Clematis rehderiana Craib on uric acid level in mice with acute hyperuricemia and the mechanism of its active ingredient in reducing uric acid. Methods Seventy Kunming mice were randomly divided into 7 groups according to their weights,including blank group,acutely high uric acid model group,allopurinol group (10 mg·kg^-1),total extract of C. rehderiana high and low dose groups (2.34,1.17 g·kg^-1),calcoside D high and low dose groups (50,20 mg·kg^-1),10 mice in each group. The mice were continuously intragastrically administered for 7 days, and the acute hyperuricemia model was induced by injection of 350 mg·kg- potassium oxonate 30 min before the last administration. Serum uric acid (UA),hepatic xanthine oxidase (XOD) levels in the C. rehderiana total extract groups,and serum UA,tumor necrosis factor α (TNF-α),interleukin-1β (IL-1β),urea nitrogen (BUN) content and liver XOD,adenosine deaminase (ADA) activity,relative expression of renal transporter mURAT1,mOAT1,and mGLUT9 mRNA in the caloside D groups were detected. Results Compared with the model group, the high and low dose groups of C. rehderiana Craib ethanol extract and the high and low dose group of calcoside D can significantly reduce the serum UA level and inhibit the activity of liver XOD (P < 0.05);and the calcoside D high and low dose groups can significantly decrease the serum levels of BUN and IL-1β (P < 0.05) . The high dose of calcoside D could significantly reduce the content of TNF-α (P < 0.05) . The high and low doses of calcoside D could inhibit the activity of liver ADA (P < 0.01) and down-regulate the mURAT1 in kidney tissue (P < 0.01),up-regulated the expression of mOAT1 mRNA (P < 0.001). Low dose of calcoside D significantly down-regulated the expression of mGLUT9 mRNA in kidney tissue (P < 0.001). Conclusion Both C. rehderiana Craib ethanol extract and calcoside D have significant UA lowering effects,and calcoside D has renal protective and anti-inflammatory effects,inhibits XOD and ADA activities, down- regulates mURAT1 and mGLUT9 mRNA expression in the kidney, and up- regulates mOAT1 mRNA expression,which is the possible mechanism of UA lowering.