Medical Physiology Department, Faculty of Medicine, Zagazig University, Alsharquiah, 44519, Egypt.
Human Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Alsharquiah, 44519, Egypt.
Pflugers Arch. 2023 May;475(5):655-666. doi: 10.1007/s00424-023-02804-0. Epub 2023 Apr 5.
A prevalent clinical problem including sepsis, shock, necrotizing enterocolitis, and mesenteric thrombosis is intestinal ischemia/reperfusion (I/R) injury. Humanin (HN), a recently identified mitochondrial polypeptide, exhibits antioxidative and antiapoptotic properties. This work aimed to study the role of HN in a model of experimental intestinal I/R injury and its effect on associated dysmotility. A total of 36 male adult albino rats were allocated into 3 equal groups. Sham group: merely a laparotomy was done. I/R group: for 1 h, clamping of the superior mesenteric artery was done, and then reperfusion was allowed for 2 h later. HN-I/R group: rats underwent ischemia and reperfusion, and 30 min before the reperfusion, they received an intraperitoneal injection of 252 μg/kg of HN. Small intestinal motility was evaluated, and jejunal samples were got for biochemical and histological analysis. I/R group showed elevation of intestinal NO, MDA, TNF- α, and IL-6 and decline of GPx and SOD levels. Furthermore, histologically, there were destructed jejunal villi especially their tips and increased tissue expression of caspase-3 and i-NOS, in addition to reduced small intestinal motility. Compared to I/R group, HN-I/R group exhibited decrease intestinal levels of NO, MDA, TNF- α, and IL-6 and increase GPx and SOD. Moreover, there was noticeable improvement of the histopathologic features and decreased caspase-3 and iNOS immunoreactivity, beside enhanced small intestinal motility. HN alleviates inflammation, apoptosis, and intestinal dysmotility encouraged by I/R. Additionally, I/R-induced apoptosis and motility alterations depend partly on the production of nitric oxide.
一种常见的临床问题,包括败血症、休克、坏死性小肠结肠炎和肠系膜血栓形成,是肠缺血/再灌注(I/R)损伤。Humanin(HN),一种最近发现的线粒体多肽,具有抗氧化和抗凋亡作用。本研究旨在研究 HN 在实验性肠 I/R 损伤模型中的作用及其对相关运动障碍的影响。总共 36 只成年雄性白化大鼠被分为 3 组。假手术组:仅进行剖腹手术。I/R 组:夹闭肠系膜上动脉 1 小时,然后再允许再灌注 2 小时。HN-I/R 组:大鼠经历缺血和再灌注,再灌注前 30 分钟,给予 252μg/kg 的 HN 腹腔内注射。评估小肠运动,获取空肠样本进行生化和组织学分析。I/R 组表现出肠道 NO、MDA、TNF-α和 IL-6 的升高,以及 GPx 和 SOD 水平的降低。此外,组织学上,空肠绒毛特别是其尖端受损,组织中 caspase-3 和 i-NOS 的表达增加,同时小肠运动减少。与 I/R 组相比,HN-I/R 组肠道 NO、MDA、TNF-α和 IL-6 水平降低,GPx 和 SOD 水平升高。此外,还观察到组织病理学特征的明显改善,caspase-3 和 iNOS 免疫反应性降低,同时小肠运动增强。HN 减轻了 I/R 引起的炎症、凋亡和肠道运动障碍。此外,I/R 诱导的凋亡和运动改变部分依赖于一氧化氮的产生。