Department of Emergency Medicine, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China.
Kidney Blood Press Res. 2021;46(3):257-265. doi: 10.1159/000509933. Epub 2021 Apr 28.
INTRODUCTION/AIMS: Hydrogen sulfide (H2S) is considered to be the third most important endogenous gasotransmitter in organisms. GYY4137 is a long-acting donor for H2S, a gas transmitter that has been shown to prevent multi-organ damage in animal studies. We previously reported the effect of GYY4137 on cardiac ischaemia reperfusion injury (IRI) in diabetic mice. However, the role and mechanism of GYY4137 in renal IRI are poorly understood. The aims of this study were to determine whether GYY4137 can effectively alleviate the injury induced by renal ischaemia reperfusion and to explore its possible mechanism.
Mice received right nephrectomy and clipping of the left renal pedicle for 45 min. GYY4137 was administered by intraperitoneal injection for 2 consecutive days before the operation. The model of hypoxia/reoxygenation injury was established in HK-2 cells, which were pre-treated with or without GYY4137. Renal histology, function, apoptosis, and oxidative stress were measured. Western blot was used to measure the target -protein after renal IRI.
The results indicated that GYY4137 had a clear protective effect on renal IRI as reflected by the attenuation of renal dysfunction, renal tubule injury, and apoptosis. Moreover, GYY4137 remarkably reduced renal IRI-induced oxidative stress. GYY4137 significantly elevated the nuclear translocation of nuclear factor-erythroid-2-related factor 2 (Nrf2) and the expression of antioxidant enzymes regulated by Nrf2, including SOD, HO-1, and NQO-1.
GYY4137 alleviates ischaemia reperfusion-induced renal injury through activating the antioxidant effect mediated by Nrf2 signalling.
简介/目的：硫化氢（H2S）被认为是生物体内第三重要的内源性气体递质。GYY4137 是 H2S 的一种长效供体，作为一种气体递质，已被证明可防止动物研究中的多器官损伤。我们之前曾报道过 GYY4137 对糖尿病小鼠心脏缺血再灌注损伤（IRI）的作用。然而，GYY4137 在肾 IRI 中的作用和机制尚不清楚。本研究旨在确定 GYY4137 是否能有效减轻肾缺血再灌注引起的损伤，并探讨其可能的机制。
小鼠接受右肾切除术和左肾蒂夹闭 45 分钟。在手术前连续两天通过腹腔注射给予 GYY4137。用 HK-2 细胞建立缺氧/复氧损伤模型，并用或不用 GYY4137 预处理。测量肾组织学、功能、细胞凋亡和氧化应激。用 Western blot 测定肾 IRI 后的靶蛋白。
结果表明，GYY4137 对肾 IRI 有明显的保护作用，表现为肾功能不全、肾小管损伤和细胞凋亡的减轻。此外，GYY4137 显著降低了肾 IRI 诱导的氧化应激。GYY4137 显著增加了核因子-红细胞 2 相关因子 2（Nrf2）的核转位和 Nrf2 调节的抗氧化酶的表达，包括 SOD、HO-1 和 NQO-1。
GYY4137 通过激活 Nrf2 信号介导的抗氧化作用减轻缺血再灌注引起的肾损伤。
