萆薢总皂苷对慢性高尿酸血症大鼠尿酸排泄指标的影响

Effect of Total Saponin of Dioscorea on Uric Acid Excretion Indicators in Chronic Hyperuricemia Rats

目的研究萆薢总皂苷(total saponin of dioscorea,TSD)对慢性高尿酸血症大鼠尿酸排泄指标的影响以及血尿酸(SUA)水平与尿酸排泄指标之间的相关性。方法 90只雄性SD大鼠随机分为正常组,模型组,TSD高、中、低剂量组(300、100、30 mg/kg)及苯溴马隆(10 mg/kg)组,每组15只。以氧嗪酸钾加乙胺丁醇制备慢性高尿酸血症模型。大鼠自由饮水、饮食,从第3周开始灌胃给药,每天1次,连续4周,分别于14、28 d测定SUA、血肌酐(SCr)、血尿素氮(BUN)、尿量(UV)、尿尿酸(UUA)、尿肌酐(UCr)含量,计算尿酸排泄指标[包括:24 h尿酸排泄量(24 h UUA)、尿酸排泄分数(FEUA)、尿酸清除率(CUr)、肌酐清除率(CCr)、单位肾小球滤过尿酸排泄(EurGF)及UUA与UCr比值(UUA/UCr)]。采用Pearson相关分析,对SUA与尿酸排泄指标之间的相关性进行分析。结果模型组大鼠14、28 d SUA、SCr均显著升高,UUA、24 h UUA、CCr、CUr、FEUA、EurGF、UUA/UCr均显著降低。TSD能剂量依赖性地降低高尿酸血症大鼠SUA,显著增加UUA、24 h UUA、CCr、CUr、FEUA及EurGF,其作用与苯溴马隆相近。TSD对高尿酸血症大鼠BUN、UCr、UUA/UCr和UV均无明显影响。相关性分析显示:给药14 d和28 d,SUA水平与SCr呈正相关(r=0.359,r=0.306),与CUr、FEUA、CCr呈显著负相关(r=-0.749,-0.733;r=-0.669,-0.646;r=-0.359,-0.273),与EurGF、UUA/UCr之间无明显相关性(r=0.134,0.078;r=-0.057,-0.065);14 d SUA与24 h UUA呈负相关(r=-0.267),与UUA、UCr之间无相关性;28 d SUA与UUA、UCr呈负相关(r=-0.269,r=-0.275),与24 h UUA之间无相关性。结论TSD可促进尿酸排泄,显著提高尿酸排泄指标;SUA水平与SCr呈正相关,与CUr、FEUA、CCr呈显著负相关;FEUA和CUr是肾脏排泄尿酸的敏感指标。

Objective To investigate the effect of total saponin of dioscorea （TSD） on uric acid excretion indicators in chronic hyperuricemia rats, and to study the correlation between blood levels of u- ric acid （SUA） and uric acid excretion indicators. Methods Totally 90 SD male rats were randomly di- vided into 6 groups, i.e., the normal group, the model group, the benzbromarone group （10 mg/kg）, the high, middle, and low dose TSD group （300,100,30 mg/kg, respectively）, 15 in each group. The chron- ic hyperuricemia model was prepared by potassium oxonate （200 mg/kg） and ethambutol （250 mg/kg） except in those of the normal group. All rats were intragastrically administered with corresponding medi- cation once daily for 4 successive weeks since the third week. Contents of SUA and urine uric acid （UUA）, serum creatinine （SCr）, urine creatinine （UCr）, blood urea nitrogen （BUN）, and urine volume （UV） were measured on day 14 and day 28 respectively. Uric acid excretion indicators [ including the a- mount of 24 h uric acid excretion （24 h UUA）, fractional excretion of uric acid （FEUA）, uric acid clearance （CUr）, creatinine clearance （COr）, excretion of uric acid per volume of glomerular filtration （Eu- rGF）, and ratio of urinary uric acid to creatinine （UUA/UCr） ~ were calculated. The correlation between SUA and uric acid excretion indicators was analyzed by Pearson correlation analysis. Results Contents of SUA and SCr significantly increased, while the UUA, 24 h UUA, CCr, CUr, FEUA, EurGF, and UUA/ UCr significantly decreased in the model group on day 14 and day 28. TSD could dose-dependently reduce the SUA level, significantly increase the UUA, 24 h UUA and CCr, Cur, FEUA, EurGF, showing an ap- proximate effect to that of benzbromarone. But it had no effect on BUN, UCr, UUA/UCr, or UV of hyperu- ricemia rats. Correlation analysis showed that SUA level was positively correlated with SCr on day 14 and day 28 （r =0.359, r = 0.306）, but negatively correlated with CUr, FEUA, and CCr （r = -0.749 and -0.733; r = -0.669 and -0.646; r = -0.359 and -0.273）. SUA level was not correlated with EurGF or UUA/UCr （r =0. 134 and 0.078; r = -0.057 and -0. 065）. SUA level was negatively correlated with 24 h UUA on day 14 （r = -0.267）, but not correlated with UUA or UCr on day 14. SUA level was negatively correlated with UUA and UCr on day 28 （r = -0.269,r = -0.275）, but not correlated with 24 h UUA on day 28. Conclusions TSD could promote the excretion of uric acid and significantly increase the excre- tion of uric acid indicators. SUA was positively correlated with SCr, negatively correlated with Cur, FEUA, and CCr. FEUA and CUr were sensitive indicators of renal excretion of uric acid.