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解析杜仲对小鼠和大鼠抗高尿酸血症作用的分子机制。

Molecular mechanistic insight into the anti-hyperuricemic effect of Eucommia ulmoides in mice and rats.

机构信息

a National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine , Jiangxi University of Traditional Chinese Medicine , Nanchang , China.

b School of Basic Medicine, Jiangxi University of Traditional Chinese Medicine , Nanchang , China.

出版信息

Pharm Biol. 2019 Dec;57(1):112-119. doi: 10.1080/13880209.2019.1568510.

DOI:10.1080/13880209.2019.1568510
PMID:30843748
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6419643/
Abstract

CONTEXT

Eucommia ulmoides Oliver (Eucommiaceae) has various medicinal properties. Our previous studies revealed that Eucommia ulmoides has a protective effect on hyperuricaemia.

OBJECTIVE

This study investigates the effect of Eucommia ulmoides cortex ethanol extract (EU) on hyperuricaemia and explores the underlying mechanism in Kunming mice and Sprague-Dawley rats.

MATERIAL AND METHODS

Sixty mice and sixty rats were divided into normal control, hyperuricaemia, allopurinol (10 mg/kg) and three EU groups. The EU groups received intragastric EU at 80, 160, 320 mg/kg in mice and 100, 200, 400 mg/kg in rats for 7 days. Serum uric acid (SUA) was measured using a kit. mRNA and proteins were quantified by RT-qPCR and immunohistochemical assays (IHC), respectively.

RESULTS

The Maximal Tolerable Dose (MTD) of EU administered intragastrically was 18 g/kg in mice. The intermediate (160 mg/kg) and high (320 mg/kg) EU treatment significantly reduced (p < 0.05) SUA levels to 130.16 μmol/L and 109.29 μmol/L, respectively, and markedly elevated the mRNA expression of organic anion transporters 1 (OAT1) and organic anion transporters 3 (OAT3), while significantly deceasing the mRNA levels of glucose transporter 9 (GLUT9) and uric acid transporter 1 (URAT1) in the mouse kidney (p < 0.05). In hyperuricemic rats, high EU (400 mg/kg) significantly reduced SUA levels to 253.85 μmol/L, and increased OAT1 and OAT3 levels, but decreased URAT1 and GLUT9, compared to the hyperuricaemia group (p < 0.05).

DISCUSSION AND CONCLUSIONS

This study demonstrated the potential hyperuricaemia ameliorating effect of EU. Specific active ingredients in EU should be evaluated. These results are valuable for the development of antihyperuritic agents from EU.

摘要

背景

杜仲(杜仲科)具有多种药用特性。我们之前的研究表明,杜仲对高尿酸血症有保护作用。

目的

本研究旨在探讨杜仲皮乙醇提取物(EU)对高尿酸血症的影响,并探讨其在昆明小鼠和 Sprague-Dawley 大鼠中的作用机制。

材料与方法

将 60 只小鼠和 60 只大鼠分为正常对照组、高尿酸血症组、别嘌呤醇(10mg/kg)组和 3 个 EU 组。EU 组小鼠分别灌胃 EU 80、160、320mg/kg,大鼠分别灌胃 EU 100、200、400mg/kg,连续 7 天。采用试剂盒检测血清尿酸(SUA)水平。采用 RT-qPCR 和免疫组织化学(IHC)分别定量检测 mRNA 和蛋白。

结果

EU 最大耐受剂量(MTD)为 18g/kg。中剂量(160mg/kg)和高剂量(320mg/kg)EU 处理可显著降低(p<0.05)SUA 水平,分别降至 130.16μmol/L 和 109.29μmol/L,并显著上调肾脏有机阴离子转运体 1(OAT1)和有机阴离子转运体 3(OAT3)的 mRNA 表达,同时显著下调葡萄糖转运蛋白 9(GLUT9)和尿酸盐转运蛋白 1(URAT1)的 mRNA 水平(p<0.05)。在高尿酸血症大鼠中,高剂量 EU(400mg/kg)可显著降低 SUA 水平至 253.85μmol/L,同时上调 OAT1 和 OAT3 水平,下调 URAT1 和 GLUT9 水平,与高尿酸血症组相比差异有统计学意义(p<0.05)。

讨论与结论

本研究表明 EU 具有潜在的降尿酸作用。应评估 EU 中的特定活性成分。这些结果为从 EU 开发抗高尿酸血症药物提供了有价值的信息。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/f070a38969fb/IPHB_A_1568510_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/77c02203598a/IPHB_A_1568510_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/65c1c6a206c9/IPHB_A_1568510_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/ffa439e2c825/IPHB_A_1568510_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/2ac9badd9478/IPHB_A_1568510_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/a97099f0ac61/IPHB_A_1568510_F0006a_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/f070a38969fb/IPHB_A_1568510_F0007_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/77c02203598a/IPHB_A_1568510_F0001_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/65c1c6a206c9/IPHB_A_1568510_F0003_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/ffa439e2c825/IPHB_A_1568510_F0004_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/2ac9badd9478/IPHB_A_1568510_F0005_B.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/a97099f0ac61/IPHB_A_1568510_F0006a_C.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ca6c/6419643/f070a38969fb/IPHB_A_1568510_F0007_B.jpg

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