Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion).
Gypenosides Inhibits Xanthine Oxidoreductase and Ameliorates Urate Excretion in Hyperuricemic Rats Induced by High Cholesterol and High Fat Food (Lipid Emulsion).
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绞股蓝皂苷抑制黄嘌呤氧化还原酶并改善高胆固醇和高脂肪食物（脂质乳剂）引起的高尿酸血症大鼠的尿酸盐排泄
DOI：
10.12659/msm.903217
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发表时间：
2017-03-04
期刊：
影响因子：
--
通讯作者：
Lv G
中科院分区：
文献类型：
--
作者：
Pang M;Fang Y;Chen S;Zhu X;Shan C;Su J;Yu J;Li B;Yang Y;Chen B;Liang K;Hu H;Lv G
目的研究绞股蓝总皂甙（GPS）对脂肪乳剂（LE）诱导的高尿酸血症大鼠的降尿酸作用及其机制。GPS是从绞股蓝中提取的天然皂甙。材料/方法雄性SD大鼠48只，随机分为正常组、模型组、阳性对照组和GPS治疗组（两个不同剂量的GPS）。正常组给予基础饲料喂养，其余大鼠给予LE预处理。定期采集尿液和血液。采用全自动生化分析仪检测血清尿酸（SUA）、血肌酐（SCr）、尿素氮（BUN）、尿尿酸（UUA）、尿肌酐（UCr）和尿酸排泄分数（FEUA）。酶联免疫吸附试验（ELISA）检测黄嘌呤氧化酶（XOD）、腺苷脱氨酶（ADA）、鸟嘌呤脱氨酶（GDA）和黄嘌呤脱氢酶（XDH）的活性。采用免疫组织化学方法观察肾脏变化和蛋白质（URAT 1、GLUT 9和OAT 1）表达水平。采用RT-PCR检测相关mRNA的表达水平。结果GPS治疗可显著降低SUA，防止LE引起的异常体重减轻，改善肾脏病理形态学。GPS处理还降低了XOD、ADA和XDH表达水平，增加了肾脏指数和FEUA，下调了肾脏中URAT 1和GLUT 9的表达，上调了OAT 1的表达。结论GPS可能通过XOD/XDH系统降低黄嘌呤氧化还原酶，通过调节URAT 1、GLUT 9和OAT 1转运蛋白增加尿酸排泄，从而有效治疗高尿酸血症。
Background The aim of this study was to study the effects of gypenosides (GPS) on lowering uric acid (UA) levels in hyperuricemic rats induced by lipid emulsion (LE) and the related mechanisms. GPS are natural saponins extracted from Gynostemma pentaphyllum. Material/Methods Forty-eight male SD rats were randomly divided into six groups: normal, model, two positive controls, and two GPS treated groups (two different doses of GPS). The normal group rats were fed a basic diet, and the other rats were orally pretreated with LE. Urine and blood were collected at regular intervals. Full automatic biochemical analyzer was used to detect the concentration levels of serum UA (SUA), serum creatinine (SCr), BUN, and urine UA (UUA), and urine creatinine (UCr) and fractional excretion of UA (FEUA). ELISA kits were used to detect enzymes activities: xanthine oxidase (XOD), adenosime deaminase (ADA), guanine deaminase (GDA), and xanthine dehydrogenase (XDH). Immunohistochemistry was used to observe kidney changes and protein (URAT1, GLUT9, and OAT1) expression levels. RT-PCR was used to detect the relevant mRNA expression levels. Results Treatment with GPS significantly reduced the SUA, prevented abnormal weight loss caused by LE, and improved kidney pathomorphology. Treatment with GPS also decreased the levels of XOD, ADA, and XDH expression, increased the kidney index and FEUA, downregulated URAT1 and GLUT9 expression and upregulated OAT1 expression in the kidney. Conclusions GPS may be an effective treatment for hyperuricemia via a decrease in xanthine oxidoreductase through the XOD/XDH system; and via an increase in urate excretion through regulating URAT1, GLUT9, and OAT1 transporters.