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小檗碱调节高尿酸血症大鼠模型的尿酸代谢和调节肠道菌群。

Berberine Regulates the Metabolism of Uric Acid and Modulates Intestinal Flora in Hyperuricemia Rats Model.

机构信息

Department of Rheumatology, Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200062, China.

Department of Oncology, The First People's Hospital of Changzhou, Changzhou, Jiangsu, 213004, China.

出版信息

Comb Chem High Throughput Screen. 2023;26(11):2057-2066. doi: 10.2174/1386207326666221124093228.

Abstract

BACKGROUND

Intestinal microbiota is the primary target for the multifunctional nature of berberine. Berberine can reverse the structure and composition of gut microbiota under pathological conditions. This study aimed to investigate the effects of berberine on uric acid (UA) metabolism and gut microbiota in a hyperuricemia rat model established using potassium oxonate.

METHODS

Sprague-Dawley (SD) male rats were divided into a normal control group (n= 10), a hyperuricemia group (n = 12) and a berberine-treated group (n = 11). The UA level in serum, urine and fecal, blood xanthine oxidase (XOD), and urate transports ABCG2 and Galectin-9 in the liver and colon, were evaluated using ELISA kits. The alterations in gut microbiota were investigated using 16S rRNA sequencing.

RESULTS

The UA level in the hyperuricemia group was significantly elevated (p<0.001), suggesting that the model was successfully established. After treatment with berberine, levels of blood and fecal UA significantly decreased (p<0.001), but not uric UA. The blood XOD level decreased, urate transport ABCG2 in the colon increased, and urate transport Galectin-9 in the colon decreased after berberine treatment (p<0.05). Further 16S sequencing revealed that berberine affected the gut microbiota composition and diversity in hyperuricemia rats. Berberine treatment reduced the relative abundance of Bacteroidetes, and increased the relative abundance of Lactobacillus. The gut microbiota were predicted to be involved in multiple metabolic pathways, such as sphingolipid metabolism, starch and sucrose metabolism and N-glycans.

CONCLUSION

Berberine might be a possible therapeutic candidate in hyperuricemia, which could regulate UA metabolism by affecting XOD, and urate transports and partly by regulating gut microbiota.

摘要

背景

肠道微生物群是小檗碱多功能性质的主要靶点。小檗碱可以在病理条件下逆转肠道微生物群的结构和组成。本研究旨在探讨小檗碱对氧嗪酸钾诱导的高尿酸血症大鼠模型尿酸(UA)代谢和肠道微生物群的影响。

方法

将 Sprague-Dawley(SD)雄性大鼠分为正常对照组(n=10)、高尿酸血症组(n=12)和小檗碱治疗组(n=11)。采用 ELISA 试剂盒检测血清、尿液和粪便中 UA 水平、血液黄嘌呤氧化酶(XOD)、肝脏和结肠中尿酸转运体 ABCG2 和半乳糖凝集素-9。采用 16S rRNA 测序分析肠道微生物群的变化。

结果

高尿酸血症组 UA 水平显著升高(p<0.001),表明模型成功建立。小檗碱治疗后,血、便 UA 水平显著降低(p<0.001),但尿 UA 水平无变化。血 XOD 水平降低,结肠中尿酸转运体 ABCG2 增加,结肠中尿酸转运体 Galectin-9 降低(p<0.05)。进一步的 16S 测序显示,小檗碱影响了高尿酸血症大鼠的肠道微生物群组成和多样性。小檗碱治疗降低了厚壁菌门的相对丰度,增加了乳杆菌属的相对丰度。肠道微生物群被预测参与多种代谢途径,如鞘脂代谢、淀粉和蔗糖代谢以及 N-聚糖。

结论

小檗碱可能是高尿酸血症的一种潜在治疗候选药物,通过影响 XOD 和尿酸转运体,部分通过调节肠道微生物群来调节 UA 代谢。

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