摘要
目的研究二妙丸水提取物对高尿酸血症小鼠尿酸失衡及其相关基因和蛋白水平的影响。方法用氧嗪酸钾盐诱导小鼠以建立高尿酸血症模型。二妙丸(3.9、7.8g/kg)、黄柏(1.95、3.9g/kg)和苍术(1.95、3.9g/kg)各水提取物分别连续ig给予小鼠1周,末次给药1h后,分别测定小鼠血清、肝脏和尿液中尿酸水平,测定血肌酐(SCr)和尿肌酐(UCr)水平及肝脏黄嘌呤氧化酶(XOD)活性;采用RT-PCR方法测定小鼠肝脏XOD和肾脏尿酸盐重吸收转运子mURAT1 mRNA表达水平;利用Western Blotting方法测定小鼠肝脏XOD和肾脏mURAT1蛋白水平。结果与模型组比较,二妙丸水提取物低、高剂量和黄柏水提取物高剂量均显著降低血清和肝脏尿酸水平,及SCr水平,增加尿液中尿酸水平和UCr水平。二妙丸和黄柏水提取物2个剂量均显著抑制肝脏XOD活性,下调XOD mRNA和蛋白表达,降低肾脏mURAT1 mRNA和蛋白表达水平。而苍术水提取物2个剂量对上述指标均无显著影响。结论二妙丸水提取物具有抑制高尿酸血症小鼠尿酸生成和促进尿酸排泄的双重调节作用,以降低血清尿酸水平,其机制可能与抑制XOD与mURAT1 mRNA和蛋白表达水平有关。
Objective To investigate the effects of Ermiao Pill water extracts on imbalance of urate levels and its related genes and protein levels in hyperuricemic mice. Methods A mouse model of hyperurieemia was established by oxygen hydroehloride acid potassium salt. The water extracts of Ermiao Pill （3.9 and 7.8 g/kg）, Cortex Phellodendri Chinensis （1.95 and 3.9 g/kg）, and Rhizoma Atractylodis （1.95 and 3. 9 g/kg） were ig administered in a volume of 15 mL/kg once daily to the different groups of animals continuously for one week, respectively. One hour after the final treatment, the urate levels in serum, urinary, and liver, as well as the creatinine Ievels in serum and urinary, and the hepatic xanthine oxidase （XOD） activity were measured. Expressions of hepatic XOD mRNA and renal mURAT1 mRNA were analyzd by semi-quantita- tive RT-PCR method and their protein levels were assayed by Western blotting method. Results Compared to vehicle-model group, Ermiao Pill water extracts at two doses and Corteac Phellodendri Chinensis at high dose significantly reduced serum uric acid, liver uric acid, and serum creatinine levels, elevated urinary uric acid, and creatinine levels. In addition, The water extracts of Ermiao Pill and Cortex Phellodendri Chinensis at two doses remarkably inhibited hepatic XOD activity, down-regulated its mRNA and pro- tein levels, and suppressed mRNA and protein levels of renal mURAT1. However, Rhizoma Atractylodis at two doses had no significant effects in the present study. Conclusion Ermiao Pill water extracts process bidirectional actions of inhibiting the production of hepatic uric acid and promoting the excretion of urinary uric acid, resulting in serum urate reduction in hyperuricemic mice. The mechanisms might be involved in down-regulation of mRNA and protein levels of hepatic XOD and renal mURAT1.
出处
《中草药》
CAS
CSCD
北大核心
2010年第3期418-423,共6页
Chinese Traditional and Herbal Drugs
基金
教育部2006年新世纪优秀人才支持计划项目(NCET-06-0442)
