Department of Radiation Oncology, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Department of Pediatrics, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA.
Physiol Rep. 2023 Aug;11(15):e15773. doi: 10.14814/phy2.15773.
Hypoxic ischemic encephalopathy (HIE) occurs in 2-5/1000 births, with acute kidney injury (AKI) occurring in 40%. AKI increases morbidity and mortality. Caffeine, an adenosine receptor antagonist, and photobiomodulation (PBM), working on cytochrome c oxidase, are potential treatments for AKI. To examine effects of caffeine and PBM on AKI in rats, Day 7 pups underwent a HIE intervention (Modified Rice-Vannucci model) replicating pathology observed in humans. Caffeine was administered for 3 days and/or PBM for 5 days following HIE. Weights and urine for biomarkers (NGAL, albumin, KIM-1, osteopontin) were collected prior to HIE, daily post intervention and at sacrifice. Both treatments reduced kidney injury seen on electron microscopy, but not when combined. HIE elevated urinary NGAL and albumin on Days 1-3 post-HIE, before returning to control levels. This elevation was significantly reduced by PBM or caffeine. KIM-1 was significantly elevated for 7 days post-HIE and was reduced by both treatments. Osteopontin was not altered by HIE or the treatments. Treatments, individually but not in combination, improved HIE-induced reductions in the enzymatic activity of mitochondrial complexes II-III. PBM and caffeine also improved weight gain. PBM and caffeine reduces AKI diagnosed by urinary biomarkers and confirmed by EM findings.
缺氧缺血性脑病（HIE）发生在每 2-5/1000 例出生中，其中 40%发生急性肾损伤（AKI）。AKI 增加发病率和死亡率。咖啡因是一种腺苷受体拮抗剂，光生物调节（PBM）作用于细胞色素 c 氧化酶，是 AKI 的潜在治疗方法。为了研究咖啡因和 PBM 对 HIE 大鼠 AKI 的影响，第 7 天的幼鼠接受了 HIE 干预（改良 Rice-Vannucci 模型），模拟了人类观察到的病理学。HIE 后给予咖啡因 3 天和/或 PBM 5 天。在 HIE 之前、干预后每天以及在牺牲时收集体重和尿液用于生物标志物（NGAL、白蛋白、KIM-1、骨桥蛋白）。两种治疗方法都减轻了电镜下观察到的肾脏损伤，但联合使用时没有减轻。HIE 在 HIE 后第 1-3 天升高了尿 NGAL 和白蛋白，然后恢复到对照水平。PBM 或咖啡因显著降低了这种升高。KIM-1 在 HIE 后 7 天显著升高，并被两种治疗方法降低。骨桥蛋白不受 HIE 或治疗的影响。单独治疗而不是联合治疗可改善 HIE 引起的线粒体复合物 II-III 酶活性降低。PBM 和咖啡因还改善了体重增加。PBM 和咖啡因可减少通过尿生物标志物诊断的 AKI，并通过 EM 结果得到证实。
