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非布司他除了在链脲佐菌素诱导的糖尿病大鼠中发挥降尿酸作用外,还能减轻肾脏损伤。

Febuxostat Attenuates Renal Damage besides Exerting Hypouricemic Effect in Streptozotocin-Induced Diabetic Rats.

作者信息

Ran Jianmin, Xu Gang, Ma Huixuan, Xu Hailing, Liu Yan, Tan Rongshao, Zhu Ping, Song Jun, Lao Gancheng

机构信息

Department of Endocrinology, Guangzhou Red Cross Hospital, Medical School of Jinan University, No. 396 Tong Fu Zhong Road, Guangzhou, China.

Guangzhou Institute of Disease-Oriented Nutritional Research, Guangzhou Red Cross Hospital, Medical School of Jinan University, No. 396 Tong Fu Zhong Road, Guangzhou, China.

出版信息

Int J Nephrol. 2017;2017:2739539. doi: 10.1155/2017/2739539. Epub 2017 Apr 19.

Abstract

. In this study, we aimed to investigate the effects of febuxostat, a novel inhibitor of xanthine oxidase (XO), on renal damage in streptozotocin- (STZ-) induced diabetic rats. . Diabetes was induced by the intraperitoneal injection of STZ in male Sprague-Dawley rats. Sham-injected rats served as controls. The control and diabetic rats were treated with and without febuxostat for 8 weeks, respectively. Fasting blood and 24-h urine samples were collected every 4 weeks. Rat livers were extracted for detecting gene expression, content, and bioactivity of XO. . Diabetic rats showed significantly increased serum uric acid (SUA), serum creatinine (SCr), and urea nitrogen (BUN) levels. Daily urinary albumin (UAE), uric acid (UUA), and creatinine (UCr) excretion were also significantly increased in these rats. In diabetic rats, at week 8, febuxostat decreased SUA by 18.9%, while UAA was increased by 52.0%. However, UCr and urinary urea nitrogen (UUN) levels remained unchanged, while SCr and BUN levels decreased by >30% in these rats. Although hepatic gene expression, content, and activity of XO increased significantly in diabetic rats, febuxostat only slightly decreased its content. . Febuxostat significantly attenuated renal damage in STZ-induced diabetic rats in addition to exerting hypouricemic effect.

摘要

在本研究中,我们旨在探究新型黄嘌呤氧化酶(XO)抑制剂非布司他对链脲佐菌素(STZ)诱导的糖尿病大鼠肾脏损伤的影响。通过对雄性Sprague-Dawley大鼠腹腔注射STZ诱导糖尿病。假注射大鼠作为对照。对照大鼠和糖尿病大鼠分别接受或不接受非布司他治疗8周。每4周采集空腹血液和24小时尿液样本。提取大鼠肝脏以检测XO的基因表达、含量和生物活性。糖尿病大鼠的血清尿酸(SUA)、血清肌酐(SCr)和尿素氮(BUN)水平显著升高。这些大鼠的每日尿白蛋白(UAE)、尿酸(UUA)和肌酐(UCr)排泄量也显著增加。在糖尿病大鼠中,第8周时,非布司他使SUA降低了18.9%,而UAA增加了52.0%。然而,UCr和尿尿素氮(UUN)水平保持不变,而这些大鼠的SCr和BUN水平降低了>30%。尽管糖尿病大鼠肝脏中XO的基因表达、含量和活性显著增加,但非布司他仅使其含量略有降低。非布司他除发挥降尿酸作用外,还显著减轻了STZ诱导的糖尿病大鼠的肾脏损伤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4ee1/5414495/2cb7f5d8916d/IJN2017-2739539.001.jpg

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