不同方法建立高尿酸合并非酒精性脂肪肝模型的对比研究

Establishment of Rat Model of Hyperuricemia Combined with Nonalcoholic Fatty Liver Disease

目的利用改良的高酵母高脂饲料喂养联合氧嗪酸钾灌胃或氧嗪酸钾皮下注射,建立高尿酸血症合并非酒精性脂肪性肝病大鼠模型。方法 48只雄性SD大鼠随机分为正常对照组(A组)、高脂饲料对照组(B组)、高酵母高脂饲料+氧嗪酸钾灌胃组(C组)、高酵母高脂饲料+氧嗪酸钾皮下注射组(D组),每组12只,造模12周,观察各组大鼠一般状况、体质量、肝湿重及血清尿酸(UA)等生化指标,并分析肝脏病理变化。结果 C、D组肝湿重明显高于A组;C组肝湿重与B组比较,差异无统计学意义;D组肝湿重明显低于B组。C、D组血清UA、CHO、TG、ALT和AST水平均明显高于A组,血清BUN与A、B组比较,差异无统计学意义;C、D组血清CREA水平明显高于A组,但与B组比较,差异无统计学意义。C、D组肝组织脂肪变性及炎性反应较A组增多。各组大鼠肾组织均无明显病变。结论利用高酵母高脂饲料喂养联合氧嗪酸钾灌胃或氧嗪酸钾皮下注射,成功了建立高尿酸血症合并非酒精性脂肪性肝病大鼠模型,与人类发病特征相似,且无明显的肾脏损害,可作为高尿酸血症合并非酒精性脂肪性肝病的的动物模型。

OBJECTIVE： To establish a rat model of hyperuricemia combined with nonalcoholic fatty liver disease by feeding modified high yeast high fat diet with oxonic acid potassium intragastric administration or subcutaneous injection. METHODS Forty-eight male SD rats were randomly divided into 4 groups： normal control group（Group A）, high-fat control group（Group B）, high yeast high fat diet with oxonic acid potassium salt intragastric administration group（Group C）, high yeast high fat diet with oxonic acid potassium salt subcutaneous injection group（Group D）, 12 rats in each group. Body mass, liver wet weight, UA, CHO, TG, ALT, AST, BUN and CREA were respectively observed in each group. And the pathological changes were analyzed. RESULTS After molding, the liver wet weight of the rats in Group C and Group D was significantly higher than that of Group A. The liver wet weight of Group C and Group B had no statistical difference（P0.05）. The liver wet weight of the rats in Group D was significantly lower than that of Group B（P0.01）. UA, CHO, TG, ALT, AST and CREA were significantly decreased after molding（P0.05）, but BUN was similar to Group A（P0.05）. Besides, after molding, range of fatty degeneration and inflammatory reaction in the liver tissue were increased compared with the Group A（P0.01）. While compared with Group A, there was no significant lesion in the renal tissue of rats after molding（P0.05）. CONCLUSION A rat model of hyperuricemia combined with nonalcoholic fatty liver disease was established successfully with no obvious kidney damage, which is similar to human pathogenesis and provide a more targeted animal model for the study of high uric acid combined with nonalcoholic fatty liver disease.