Jiang Guanjun, Wang Min, Wang Lei, Chen Hui, Chen Zhiyuan, Guo Jia, Weng Xiaodong, Liu Xiuheng
a Department of Urology , Renmin Hospital of Wuhan University , Wuhan , Hubei , PR China.
Ren Fail. 2015 Jun;37(5):882-9. doi: 10.3109/0886022X.2015.1015426. Epub 2015 Feb 24.
The pathogenetic mechanisms underlying ischemia-reperfusion (I/R) injury involve oxidative stress, inflammation and apoptosis. Nesfatin-1, a novel peptide, has been reported to possess antioxidant, anti-inflammatory and anti-apoptic properties. The study was to examine the potential protective effects of nesfatin-1 on renal I/R injury.
I/R model was induced by placing a clamp across left renal artery for 45 min followed by 24 h reperfusion, along with a contralateral nephrectom. Twenty-four rats divided into three groups: sham-operated group, vehicle-treated I/R and nesfatin-1-treated I/R. Nesfatin-1 was intraperitoneally injected 30 min before renal ischemia. We harvested serum and kidneys at 24 h after reperfusion. Renal function and histological changes were assessed. Marker of oxidative stress and cells in kidney were also evaluated.
The animals with nesfatin-1 significantly improved renal functional and histologic lesions induced by I/R injury. The malondialdehyde (MDA) level decreased, whereas superoxide dismutase (SOD) and catalase (CAT) activities were significantly increased. Moreover, nesfatin-1-treated rats had a markedly decrease in apoptotic tubular cells, as well as a decrease in caspase-3 activity and an increase in the bcl-2/Bax ratio.
This is the first evidence that nesfatin-1 treatment ameliorates acute renal I/R injury by suppressing oxidative stress and cell apoptosis. Therefore, it is promising as a potential therapeutic agent for renal IR injury.
缺血再灌注(I/R)损伤的发病机制涉及氧化应激、炎症和细胞凋亡。Nesfatin-1是一种新型肽,据报道具有抗氧化、抗炎和抗凋亡特性。本研究旨在探讨Nesfatin-1对肾I/R损伤的潜在保护作用。
通过夹闭左肾动脉45分钟,然后再灌注24小时,同时进行对侧肾切除术,诱导建立I/R模型。将24只大鼠分为三组:假手术组、溶剂处理的I/R组和Nesfatin-1处理的I/R组。在肾缺血前30分钟腹腔注射Nesfatin-1。再灌注24小时后收集血清和肾脏。评估肾功能和组织学变化。还评估了肾脏氧化应激标志物和细胞情况。
接受Nesfatin-1治疗的动物,其因I/R损伤引起的肾功能和组织学损伤得到显著改善。丙二醛(MDA)水平降低,而超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活性显著升高。此外,接受Nesfatin-1治疗的大鼠肾小管凋亡细胞明显减少,同时半胱天冬酶-3活性降低,bcl-2/Bax比值升高。
这是首个表明Nesfatin-1治疗可通过抑制氧化应激和细胞凋亡改善急性肾I/R损伤 的证据。因此,它有望成为肾I/R损伤的潜在治疗药物。