Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Minerva Institute for Medical Research, Biomedicum Helsinki 2U, Helsinki, Finland.
Basic Clin Pharmacol Toxicol. 2023 Jan;132(1):21-32. doi: 10.1111/bcpt.13806. Epub 2022 Oct 21.
Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 μmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.
尿酸在实验研究中促进了肾纤维化和炎症，但一些研究表明由于氧化应激减轻而具有肾保护作用。我们研究了实验性高尿酸血症对手术性 5/6 肾切除大鼠的影响。在部分肾切除或假手术 3 周后，大鼠被分配到对照饮食或 2.0% 氧嗪酸钾（尿酸酶抑制剂）饮食 9 周。然后采集血液、尿液和组织样本，检查肾脏形态和氧化应激。使用免疫组织化学和实时 PCR（RT-PCR）评估炎症和纤维化。摄取正常或氧嗪酸钾饮食的残余肾脏大鼠的肌酐清除率降低了约 60%，血浆肾素活性受到抑制。氧嗪酸钾饮食使血浆尿酸水平升高超过 80μmol/L。在残余肾脏大鼠中，适度高尿酸血症可减少肾小球硬化、肾小管间质损伤和肾脏肥大细胞计数，而不会影响纤维化标志物胶原 I 信使 RNA（mRNA）含量。在假手术和 5/6 肾切除大鼠中，尿中 11-epi-前列腺素-F 排泄和肾组织环氧化酶-2（COX-2）水平的肥大细胞产物降低。总之，高尿酸血症性残余肾脏大鼠的肾脏形态改善，氧化应激和炎症标志物减少。因此，在这种低肾素实验性肾功能不全模型中，适度升高的血浆尿酸对肾脏具有有益作用。
