Department of Anesthesiology, Second Hospital of Shanxi Medical University, Taiyuan, China.
Department of Anesthesiology, The Affiliated Hospital of Yan'an University, Yan'an, China.
Biol Res. 2020 Jul 3;53(1):28. doi: 10.1186/s40659-020-00297-0.
Kidney ischemia-reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia-reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism.
Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement.
The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia-reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia-reperfusion-induced loss of kidney ΔΨm.
Our findings indicate that EDA protects against kidney damage caused by ischemia-reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
肾缺血再灌注损伤是临床常见的病理生理现象。大量研究发现，酪氨酸蛋白激酶/信号转导子和转录激活子（JAK/STAT）通路参与多种肾脏疾病的发生发展以及与多种药物相关的肾脏保护作用。依达拉奉（EDA）是一种有效的自由基清除剂，已临床用于治疗缺血性神经元损伤。本研究旨在探讨 EDA 是否通过调节 JAK/STAT 通路改善缺血再灌注损伤大鼠的肾功能，并阐明其潜在机制。
采用组织形态学分析评估肾脏病理损伤，透射电镜观察线粒体损伤，末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）染色检测肾小管上皮细胞凋亡，Western blot 检测 JAK2、P-JAK2、STAT3、P-STAT3、STAT1、P-STAT1、BAX 和 Bcl-2 的表达。通过测量线粒体膜电位（ΔΨm）评估肾脏线粒体功能。
结果表明，EDA 抑制了 p-JAK2、p-STAT3 和 p-STAT1 的表达，同时下调了 Bax 和 caspase-3 的表达，显著改善了缺血再灌注损伤引起的肾脏损伤。此外，JC-1 染料试验表明，依达拉奉减轻了缺血再灌注引起的肾脏 ΔΨm 丧失。
我们的研究结果表明，EDA 通过 JAK/STAT 信号通路抑制细胞凋亡和改善线粒体损伤，对缺血再灌注引起的肾脏损伤起保护作用。
