Education and Research Center for Clinical Pharmacy, Osaka Medical and Pharmaceutical University, Osaka 569-1094, Japan.
Department of Innovative Medicine, Osaka Medical and Pharmaceutical University, Osaka 590-0906, Japan.
Int J Mol Sci. 2021 Oct 23;22(21):11448. doi: 10.3390/ijms222111448.
Oxidative stress plays an important role in the pathophysiology of acute kidney injury (AKI). Previously, we reported that vanin-1, which is involved in oxidative stress, is associated with renal tubular injury. This study was aimed to determine whether urinary vanin-1 is a biomarker for the early diagnosis of AKI in two experimental models: in vivo and in vitro. In a rat model of AKI, ischemic AKI was induced in uninephrectomized rats by clamping the left renal artery for 45 min and then reperfusing the kidney. On Day 1 after renal ischemia/reperfusion (I/R), serum creatinine (SCr) in I/R rats was higher than in sham-operated rats, but this did not reach significance. Urinary N-acetyl-β-D-glucosaminidase (NAG) exhibited a significant increase but decreased on Day 2 in I/R rats. In contrast, urinary vanin-1 significantly increased on Day 1 and remained at a significant high level on Day 2 in I/R rats. Renal vanin-1 protein decreased on Days 1 and 3. In line with these findings, immunofluorescence staining demonstrated that vanin-1 was attenuated in the renal proximal tubules of I/R rats. Our in vitro results confirmed that the supernatant from HK-2 cells under hypoxia/reoxygenation included significantly higher levels of vanin-1 as well as KIM-1 and NGAL. In conclusion, our results suggest that urinary vanin-1 might be a potential novel biomarker of AKI induced by I/R.
氧化应激在急性肾损伤 (AKI) 的病理生理学中发挥着重要作用。此前，我们报道过参与氧化应激的 vanin-1 与肾小管损伤有关。本研究旨在确定尿 vanin-1 是否是两种实验模型（体内和体外）中 AKI 的早期诊断生物标志物。在 AKI 大鼠模型中，通过夹闭左肾动脉 45 分钟然后再灌注肾脏，对单侧肾切除大鼠诱导缺血性 AKI。在肾缺血/再灌注 (I/R) 后第 1 天，I/R 大鼠的血清肌酐 (SCr) 高于假手术大鼠，但无统计学意义。尿 N-乙酰-β-D-氨基葡萄糖苷酶 (NAG) 表现出显著增加，但在 I/R 大鼠中第 2 天下降。相比之下，尿 vanin-1 在第 1 天显著增加，并在 I/R 大鼠中第 2 天仍保持显著高水平。肾 vanin-1 蛋白在第 1 天和第 3 天减少。与这些发现一致，免疫荧光染色表明 vanin-1 在 I/R 大鼠的近端肾小管中减弱。我们的体外结果证实，缺氧/复氧条件下 HK-2 细胞的上清液中包含明显更高水平的 vanin-1 以及 KIM-1 和 NGAL。总之，我们的研究结果表明，尿 vanin-1 可能是 I/R 诱导的 AKI 的一种潜在新型生物标志物。
