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齿孔酸对高尿酸血症黄嘌呤氧化酶活性的影响
张琳,汪鋆植,余海立,汪瑾雨,苟保灵,李雨点,邹坤,苏香萍,贺海波,
1.湖北省土家族医药研究所/三峡大学天然产物研究与利用湖北省重点实验室
摘要:
采用紫外分光光度法检测齿孔酸在体外对黄嘌呤氧化酶的作用,并进行动力学研究探讨其作用机制;采用酵母联合氧嗪酸钾诱导高尿酸血症小鼠模型,观察齿孔酸对高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性及血糖血脂的影响。研究发现,齿孔酸体在外能抑制黄嘌呤氧化酶活性,降低高尿酸血症小鼠血清尿酸水平、血清黄嘌呤氧化酶活性、肝脏黄嘌呤氧化酶活性,同时明显降低空腹血糖、总胆固醇、甘油三酯、低密度脂蛋白胆固醇水平,升高高密度脂蛋白胆固醇水平,提高口服糖耐受量。结果表明,齿孔酸是黄嘌呤氧化酶竞争性抑制剂,还能缓解高尿酸血症小鼠糖脂代谢紊乱,对高尿酸血症及痛风的防治具有潜在意义。
关键词:  硫磺菌  齿孔酸  高尿酸血症  黄嘌呤氧化酶  反向筛选
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Effects of eburicoic acid on xanthine oxidase activity of hyperuricemia
ZHANG Lin,WANG Junzhi,YU Haili,WANG Jinyu,GOU Baoling,LI Yudian,ZOU Kun,SU Xiangping,HE Haibo,Hubei Research Institute of Tujia Medicine/Hubei Key Laboratory of Natural Products Research,Development,China Three Gorges University
Hubei Research Institute of Tujia Medicine/Hubei Key Laboratory of Natural Products Research and Development,China Three Gorges University
Abstract:
The inhibition of eburicoic acid on xanthine oxidase was assayed by ultraviolet spectrophotometry in vitro,and enzyme kinetics analysis was performed to explore its inhibition mechanism.Hyperuricemia mice model was induced by yeast and potassium oxonate,and the therapeutic effects of eburicoic acid on hyperuricemia mice were evaluated by serum uric acid,serum xanthine oxidase,hepatic xanthine oxidase and levels of serum glucose and lipid.In this study,the kinetic analysis showed that eburicoic acid had an inhibitory effect on xanthine oxidase activity in a reversible competitive manner.Treatment with eburicoic acid significantly decreased the levels of serum uric acid,serum xanthine oxidase,hepatic xanthine oxidase of hyperuricemia mice.The levels of fasting blood glucose,serum triglyceride,serum total cholesterol and serum low density lipoprotein cholesterol in eburicoic acid treated groups were decreased,and serum high density lipoprotein cholesterol and glucose tolerance were increased compared with the model group.The results showed that eburicoic acid a competitive inhibitor of xanthine oxidase,which led to uric acid reduction and relieved the metabolism disorder in hyperuricemia mice.Eburicoic acid has the potential of treating hyperuricemia and gout in clinic.
Key words:  Laetiporus sulphureus  eburicoic acid  hyperuricemia  xanthine oxidase  inversion screening