一种高尿酸血症大鼠模型诱导方法的改良和效果评价研究

The optimization and assessment of the method for inducing hyperuricemia in rats

目的:探索短期内诱导高尿酸血症大鼠模型的有效方法,并对模型效果进行评价。方法:雄性SD大鼠随机分为对照组(CT组,6只)和5个模型组(M1-M5组),每组8只;M1组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg 2次灌胃,于模型诱导的第7日1次性腹腔注射氧嗪酸钾300 mg/kg)、M2组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg灌胃2次,于模型诱导第1、3、7日每天腹腔注射1次氧嗪酸钾300 mg/kg)、M3组(每天酵母膏10 g/kg+腺嘌呤100 mg/kg灌胃2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、M4组(每天酵母膏20 g/kg+腺嘌呤100 mg/kg灌胃2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、M5组(每天酵母膏30 g/kg+腺嘌呤100 mg/kg灌胃2次,每天腹腔注射1次氧嗪酸钾300 mg/kg)、CT组(5个模型组按相同的时间、体重计算等体积灌胃和腹腔注射生理盐水),造模7 d;分别在造模结束时和2周后采集24 h尿样和血样检测尿酸、肌酐水平,取肾脏和胃称重,观察肾脏病理变化。结果:与CT组相比,造模结束后,所有模型组大鼠体重均显著降低(P<0.01);除M2组外,其他造模组大鼠均有亡,M4组和M5组因死亡率高未做后续分析,M1和M3组分别死亡4例和2例;造模结束后,模型大鼠血尿酸、尿尿酸水平明显升高(P<0.01),并且M2组的血尿酸水平显著高于其他各组(P<0.05);继续喂养2周后,各模型组的血尿酸和尿尿酸水平仍显著升高(P<0.05);各模型组大鼠肾脏重量也明显增加(P<0.01);病理检查显示,模型组大鼠肾脏出现明显炎症反应和结构破坏。结论:采用酵母膏(10 g/kg)、腺嘌呤(100 mg/kg)联合氧嗪酸钾(300 mg/kg)间隔(第1、3、7日)注射的方案可在短期内安全地诱导高尿酸血症大鼠模型,模型效果持续时间较长,适合在相关研究中应用。

Objective:To explore an effective method for inducing a rat model with hyperuricemia in a short period and assess the effects of the model.Methods:Sprague-Dawley rats were adopted as donors and randomly divided into control group(CT group,n=6)and 5 model groups(M1-M5 groups,n=8 in each group).M1 group(gavage with 10 g/kg yeast extracts and 100 mg/kg adenine,twice per day,300 mg/kg oxonic acid potassium by intraperitoneal injection,in the 7 th day of model inducing),M2 group(gavage with 10 g/kg yeast extracts and 100 mg/kg adenine,twice per day,300 mg/kg oxonic acid potassium by intraperitoneal injection,in the 1 st,3 rd and 7 th day of model inducing),M3 group(gavage with 10 g/kg yeast extracts and 100 mg/kg adenine,twice per day,300 mg/kg oxonic acid potassium by intraperitoneal injection,once per day during the model inducing),M4 group(gavage with 20 g/kg yeast extracts and 100 mg/kg adenine,twice per day,300 mg/kg oxonic acid potassium by intraperitoneal injection,once per day during the model inducing),M5 group(gavage with 30 g/kg yeast extracts and 100 mg/kg adenine,twice per day,300 mg/kg oxonic acid potassium by intraperitoneal injection,once per day during the model inducing),and group CT(gavaged with equal volume sterilized water and intraperitoneal injected with normal saline according to the weight and at the same frequency as the model groups).The model inducing lasted for 7 days.After the inducing was finished,blood and 24-hour urine were sampled for uric acid and creatinine determination.Then rats were maintained for 2 weeks and blood and 24-hour urine samples were collected,the concentration of uric acid and creatinine were detected.The kidney and stomach were weighed,morphological changes in kidney were observed.Results:After model inducing,the body weight of rats in all model groups was lower than that of the control group(P<0.01).Deaths occurred in all the rats with model treatments except M2.M4 and M5 groups were failed to be analyzed because of the high mortality,model 1 and 3 groups had 4 and 2 deaths,respectively.The uric acid levels in blood and urine of the model groups were significantly elevated(P<0.01)at the end of model inducing.The model 2 group’s blood uric acid was highest among the model groups(P<0.05).It sustained a higher concentration than CT group in the three model groups after 2 weeks feeding(P<0.05).The kidneys in model groups obviously swelling and were heavier than CT group(P<0.01).The inflammation and structural damages were observed in kidneys of all model groups.Conclusion:The yeast extract(10 g/kg),adenine(100 mg/kg)gavage combined with intraperitoneal injections(the 1 st,3 rd,7 th day during inducing)of potassium oxonate can be an rapid and effective method for inducing the rat model with hyperuricemia,which can be suggested to the related research.