基于三联法高尿酸血症小鼠模型的建立与评价
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浙江中医药大学

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国家自然科学基金(82274175);浙江省中医药管理局重点项目(GZY-ZJ-KJ-23069)


Establishment and evaluation of hyperuricemia mouse model based on triple method
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Zhejiang Chinese Medical University

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The National Natural Science Foundation of China (82274175);Key project of Zhejiang Administration of Traditional Chinese Medicine(GZY-ZJ-KJ-23069)

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    摘要:

    目的:探讨三联造模法(氧嗪酸钾、次黄嘌呤以及30%酵母膏饲料联用)能否在ICR背景小鼠上建立稳定可靠的高尿酸血症模型,并采用阳性药非布司他对该造模方法进行评价。方法:采用氧嗪酸钾、次黄嘌呤和30%酵母膏饲料,分别单用、两药或三药联用建立ICR小鼠高尿酸血症模型,检测血清尿酸、肌酐、黄嘌呤氧化酶(XOD)、尿酸氧化酶(UOX)等指标评价高尿酸血症模型成功与否。结果:氧嗪酸钾单用对ICR小鼠血清尿酸水平没有明显改变,与30%酵母膏饲料和次黄嘌呤分别联用组血尿酸有升高趋势但无显著差异,而三联给药组在7天时显著提高(P<0.01);14天的动态监测发现三联给药诱导的ICR小鼠血尿酸水平在7天时达到峰值;同时,XOD酶活性提升,UOX酶活性降低(P<0.001)。此外,三联给药诱导的ICR小鼠高尿酸血症模型对阳性药物非布司他反应敏感,血尿酸水平显著下降(P<0.001)。结论:通过三联给药的方法可以在7天时稳定诱导ICR小鼠的高尿酸血症模型。

    Abstract:

    Objective: To investigate whether a stable and reliable hyperuricemia model can be established in mice with ICR background by triple modeling method (combined with potassium oxazine, hypoxanthine and 30% yeast paste), and to evaluate the modeling method with positive drug febuxoesta. Methods: The hyperuricemia model of ICR mice was established by using potassium oxazine, hypoxanthine and 30% yeast paste diet, respectively, and the serum uric acid, creatinine, xanthine oxidase (XOD), uric acid oxidase (UOX) and other indicators were detected to evaluate the success of hyperuricemia model.Results: The serum uric acid level of ICR mice was not significantly changed by potassium oxazinate alone, which showed an increasing trend but no significant difference with that of 30% yeast paste diet and hypoxanthine combined groups, while the serum uric acid level in triple administration group was significantly increased at 7 days (P<0.01). After 14 days of dynamic monitoring, blood uric acid level of triple dose induced ICR mice peaked at 7 days. Meanwhile, the activity of XOD enzyme was increased, while that of UOX enzyme was decreased (P<0.001). In addition, triple-dose induced hyperuricemia in ICR mice was sensitive to the positive drug febuxoat, with a significant decrease in blood uric acid levels (P<0.001). Conclusion: The hyperuricemia model of ICR mice can be stably induced by triple administration at 7 days.

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  • 收稿日期:2023-05-30
  • 最后修改日期:2023-09-06
  • 录用日期:2024-02-26
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