连续高果糖饮水对大鼠尿酸水平的影响及其病理机制

Effect of high fructose drinking water on uric acid level in rats and the underlying pathological mechanism

目的 探讨长期高果糖饮水对大鼠尿酸水平的影响及其病理机制.方法 雄性SD大鼠20只,采用随机数字表法分为正常组（n=10）和模型组（n=10）,分别给予清水和10％的果糖水,均给予普通饲料,自由饮食饮水,连续58 d.动态检测大鼠血清和尿中的尿酸和肌酐水平,计算尿酸清除率（CUA）和内生肌酐清除率（CCR）,检测尿酸代谢相关酶黄嘌呤氧化酶（XOD）、腺苷脱氨酶（ADA）和鸟嘌呤脱氨酶（GuDa）活性,并观察造模结束时大鼠肾脏病理变化.结果 实验第7、22、30、37、44、58天,模型组大鼠血清尿酸水平均显著高于正常组[（81.12 ±31.06） μmol/L比（54.27±23.42）μmol/L,P=0.017; （145.82±29.66） μmol/L比（114.90±28.04） μmol/L,P=0.033; （131.16±61.93） μmol/L比（54.67 ±33.49） μmol/L,P=0.002; （110.01±42.82） μmol/L比（66.43 ±22.50） μmol/L,P=0.007; （211.60±44.31） μmol/L比（171.44±38.72）μ.mol/L,P=0.039;（102.97±45.46） μmol/L比（62.24±20.89） μmol/L,P＝0.025].与正常组比较,模型组大鼠实验第22、37天血清XOD活性显著降低[（48.19±8.04）U/L比（58.71 ±5.18） U/L,P=0.003;（60.07 ±6.53） U/L比（66.74±6.58） U/L,P=0.027];实验第37、44天血清ADA活性显著升高[（60.00±8.22） U/ml比（46.19±14.16） U/ml,P=0.048; （75.00±16.94） U/ml比（59.17±10.27） U/ml,P=0.037];实验第44天血清GuDa活性显著升高[（10.07 ±0.66）U/L比（9.33±0.71） U/L,P＝0.037].实验第44天,模型组的CUA和CCR均显著低于正常组[（0.24±0.15）ml/min比（0.40 ±0.12） ml/min,P=0.021; （0.33 ±0.21） ml/min比（0.57 ±0.27）ml/min,P=0.040].实验第58天,模型组大鼠肾小球数量减少、毛细血管壁增厚、囊腔变窄,未见异物沉积.结论 连续饮用高果糖水可引起大鼠血尿酸水平持续升高,诱发高尿酸血症.该病理现象的发生可能与果糖在体内代谢引起尿酸生成增多及尿酸经由肾脏排泄减少相关.

Objective To investigate the pathological mechanism underlying the effects of high fructose drinking water on the uric acid level in rats.Methods 20 male SD rats were randomly divided with random number table to the control group （n =10,given normal water） and the model group （n =10,given 10% fructose water）,both fed with ordinary food for 58 days.Serum and urinary uric acid （UA） and creatine levels in the rats were monitored to calculate clearance of uric acid （CUA） and endogenous creatinine clearance rate （CCR）.The activities of serum xanthine oxidase （XOD）,adenosine deaminase （ADA）,and guanine deaminase （GuDa） were detected,and pathological changes of the kidney of the rats were observed on the 58th day.Results Compared with the control group,the serum UA level of the model group was significantly higher on the 7th,22th,30th,37th,44th,58th days [（81.12 ±31.06） μmmol/L vs.（54.27 ±23.42） μmmol/L,P =0.017; （145.82±29.66） μmol/Lvs.（114.90±28.04） μmol/L,P=0.033; （131.16±61.93） μ mol/L vs.（54.67 ± 33.49） μ mol/L,P =0.002 ; （110.01 ± 42.82） μmol/L vs.（66.43 ± 22.50） μmol/L,P =0.007; （211.60±44.31） μmol/Lvs.（171.44±38.72） μmol/L,P=0.039; （102.97±45.46） μmol/L vs.（62.24 ± 20.89） μ.mol/L,P =0.025].Compared with the control group,XOD activity in the model group decreased significantly on the 22th and the 37th days [（48.19 ±8.04） U/L vs.（58.71 ±5.18） U/L,P=0.003; （60.07 ±6.53） U/L vs.（66.74 ±6.58） U/L,P=0.027] ; ADA activity in the model group increased significantly on the 37th and the 44th day [（60.00 ±8.22） U/ml vs.（46.19 ± 14.16） U/ml,P =0.048; （75.00 ± 16.94） U/ml vs.（59.17 ± 10.27） U/ml,P=0.037] ; and GuDa activity of the model group increased significantly on the 44th days [（10.07 ±0.66） U/L vs.（9.33 ±0.71） U/L,P =0.037].On the 44th day,both CUA and CCR in the model group were significantly lower than those in the control group [（0.24±0.15） ml/minvs.（0.40±0.12） ml/min,P=0.021; （0.33 ±0.21） ml/min vs.（0.57± 0.27） ml/min,P =0.040].On the 58th day,the kidneys of the rats in the model groups demonstrated decreased number of glomeruli,thickened capillary wall,and narrowed Bowman＇s capsules,but no trace of foreign substance deposition.Conclusions Continuous consumption of high fructose drinking water can increase the serum UA level and induce hyperuricemia.This pathological condition may be related to increased synthesis and decreased renal excretion of UA caused by fructose metabolilsm.