黄嘌呤氧化还原酶 (XOR) 抑制剂可能会阻止活性氧的产生，从而导致肾小球硬化。我们的目的是研究托匹司他（一种 XOR 抑制剂）是否可以预防小鼠糖尿病肾病的发展。六周大的对照癌症研究所 (ICR) 小鼠和 2 型糖尿病名古屋柴田安田 (NSY) 小鼠被分为 ICR 组（ICR 小鼠接受含猪油的高脂肪饮食 [HFD]，基于AIN-93G饮食）、NSY对照组（接受与上述相同饮食的NSY小鼠）和NSY托吡索坦组（接受与上述相同饮食但添加0.0012%托吡索坦的NSY小鼠）。 20周后，通过酶联免疫吸附测定或酶法测量血浆生物标志物、XOR活性和氧化应激水平，并使用丙二醛（MDA）进行评估。使用高碘酸希夫染色评估肾脏病理学。使用 RT-qPCR 和蛋白质印迹法测定氧化还原基因和蛋白质表达。使用托匹司他治疗的 NSY 小鼠的血浆 XOR 活性低于未治疗的小鼠。 ICR 和 NSY 对照组之间或 NSY 对照组和 NSY 托吡索坦组之间的血浆胱抑素 C 和肌酐水平没有差异。 NSY托吡索坦组显示出比NSY对照组更小的系膜面积。 NSY托匹司他组中Sod3、Prdx1、Gpx2和Gpx3的mRNA表达高于NSY对照组。 NSY 托匹司他组的肾 MDA 水平低于 HFD 对照组。托匹司他可以减少肾小球硬化，这种减少与肾脏氧化标志物有关。版权所有 © 2024。由 Elsevier B.V. 出版。

Reactive oxygen species production might be prevented by xanthine oxidoreductase (XOR) inhibitors, which can cause glomerulosclerosis. We aimed to investigate whether topiroxostat, an XOR inhibitor, prevents diabetic kidney disease development in mice. Six-week-old control Institute of Cancer Research (ICR) mice and type-2 diabetic Nagoya Shibata Yasuda (NSY) mice were divided into the ICR group (ICR mice who received a lard-containing high-fat diet [HFD] based on the AIN-93G diet), NSY control group (NSY mice who received the same aforementioned diet), and NSY+topiroxostat group (NSY mice who received the same aforementioned diet with addition of 0.0012% topiroxostat). After 20 weeks, plasma biomarkers, XOR activity and oxidative stress levels, which were assessed using malondialdehyde (MDA), were measured through enzyme-linked immunosorbent assay or enzymatic methods. Kidney pathology was evaluated using periodic acid-Schiff staining. Redox gene and protein expression were determined using RT-qPCR and western blotting. Plasma XOR activity was lower in NSY mice treated with topiroxostat than those without. Plasma cystatin C and creatinine levels did not differ between the ICR and NSY control groups or between the NSY control and NSY+topiroxostat groups. The NSY+topiroxostat group showed a smaller mesangial area than the NSY control group. The mRNA expression of Sod3, Prdx1, Gpx2, and Gpx3 was higher in the NSY+topiroxostat group than in the NSY control group. Renal MDA levels were lower in the NSY+topiroxostat group than in the HFD control group. Topiroxostat can reduce glomerular sclerosis, and the reduction is associated with renal oxidative markers.Copyright © 2024. Published by Elsevier B.V.