不同因素诱导高尿酸血症小鼠模型的比较研究
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1.浙江中医药大学药学院,杭州 310000;2.浙江中医药大学第二临床医学院,杭州 310000;3.浙江中医药大学基础医学院,杭州 310000;4.浙江中医药大学第三临床医学院,杭州 310000

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R-33

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Comparative study of hyperuricemia induced by different factors in mouse models
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1. School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310000, China.2. Second Clinical Hospital of Zhejiang Chinese Medical University, Hangzhou 310000. 3. School of Basic Medicine, Zhejiang Chinese Medical University, Hangzhou 310000. 4. Third Clinical Hospital of Zhejiang Chinese Medical University, Hangzhou 310000

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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、肌酐含量、黄嘌呤氧化酶(XOD)、尿酸氧化酶(UOX)活性,尿酸转运蛋白(URAT) 1、葡萄糖转运蛋白(Glut) 9、阴离子转运蛋白(OAT) 1、ATP 结合盒亚家族 G 成员(ABCG)2 mRNA 水平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 d 时显著提高(P<0. 01);同时,三联给药组 XOD 酶活性提升(P<0. 001),UOX 酶活性降低(P<0. 001);URAT1、Glut9 表达水平升高(P<0. 05,P<0. 001),OAT1、ABCG2 表达水平降低(P<0. 001);14 d 的动态监测发现三联给药诱导的 ICR 小鼠血尿酸水平在 7 d 时达到峰值。 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 d 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 an ICR background via a triple-modeling method ( combined potassium oxazine, hypoxanthine, and 30% yeast paste), and to evaluate the effect of the positive drug febuxostat on the model. Methods A hyperuricemia model of ICR mice was established using a single drug or double- or triple-drug combinations. Serum uric acid and creatinine concentrations, xanthine oxidase (XOD) and urate oxidase (UOX) activity, and uric acid transporter (URAT)1, glucose transporter (Glut)9, anion transporter (OAT)1, and ATP-binding box subfamily G member (ABCG)2 mRNA levels were detected to evaluate whether the hyperuricemia model was formed successfully. Results The serum uric acid levels of ICR mice were not significantly changed by potassium oxazine alone, as they showed an increase but were not significantly different to those of the 30% yeast paste diet or hypoxanthine combined groups. Serum uric acid levels in the triple administration group were significantly increased at 7 days (P<0. 01), while XOD enzyme activity had increased(P<0.01) and UOX enzyme activity decreased (P<0. 001) at the same timepoint. There were increased expression levels of URAT1 and Glut9 (P<0. 05, P< 0. 001), and decreased expression levels of OAT1 and ABCG2 (P<0. 001). During dynamic monitoring, the blood uric acid levels of triple administration-induced ICR mice peaked at 7 days. In addition,triple administration-induced hyperuricemia in ICR mice was sensitive to the positive drug febuxostat, which caused a significant decrease in blood uric acid levels ( P< 0. 001). Conclusions A hyperuricemia model in ICR mice can be stably induced by triple administration for 7 days.

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倪建宇,白宁宁,刘贤莉,龚丽红,寿旗扬.不同因素诱导高尿酸血症小鼠模型的比较研究[J].中国比较医学杂志,2024,34(3):68~74.

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  • 收稿日期:2023-05-30
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  • 在线发布日期: 2024-05-29
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