Linking renal hypoxia and oxidative stress in chronic kidney disease: Based on clinical subjects and animal models

作者：Yizeng Xu, Fang Lü, Meng Wang, Lingchen Wang, Chaoyang Ye, Shuohui Yang, Chen Wang · 发表于：Biomolecules and Biomedicine · 年份：2024 · DOI：10.17305/bb.2024.10257 · 被引用次数：9 · 研究领域：Heme Oxygenase-1 and Carbon Monoxide、MRI in cancer diagnosis、Cancer, Hypoxia, and Metabolism

The prevalence of chronic hypoxia and oxidative stress plays a key role in the progression of chronic kidney disease (CKD), but the underlying correlations between them need further elucidation. This study aims to explore the relationships between renal function, hypoxia, and oxidative stress in CKD. Seventy-six non-dialysis patients with CKD stages 1-5 and eight healthy subjects were included in the clinical research. They were divided into three groups: healthy subjects, CKD stages 1-3, and CKD stages 4-5. In the animal study, 16 rat models of CKD were established through 5/6 renal ablation/infarction (A/I) surgery, and 8 normal rats were split into 3 groups: Sham, CKD, and losartan groups. Blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI) was used to measure cortical and medullary T2* values (COT2* and MET2*) in all subjects and rats to evaluate renal oxygenation. Biochemical indicators were used to assess renal function and antioxidant capacity. Furthermore, the effects of losartan on renal fibrosis, hypoxia, and oxidative stress were examined using immunoblotting, colorimetric, and fluorometric assays. The results demonstrated significant positive associations between COT2* and MET2* with estimated glomerular filtration rate (eGFR). Patients with CKD stages 4-5 showed significantly lower serum superoxide dismutase (SOD) levels, which also had positive correlations with eGFR, COT2*, and MET2*. Furthermore, losartan treatment resulted in improved rena...