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人亲菌素在大鼠肠缺血再灌注损伤模型中对肠细胞凋亡和运动障碍的新的有益作用。

A novel beneficial role of humanin on intestinal apoptosis and dysmotility in a rat model of ischemia reperfusion injury.

机构信息

Medical Physiology Department, Faculty of Medicine, Zagazig University, Alsharquiah, 44519, Egypt.

Human Anatomy & Embryology Department, Faculty of Medicine, Zagazig University, Alsharquiah, 44519, Egypt.

出版信息

Pflugers Arch. 2023 May;475(5):655-666. doi: 10.1007/s00424-023-02804-0. Epub 2023 Apr 5.

DOI:10.1007/s00424-023-02804-0
PMID:37020079
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10105677/
Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/343868c3aded/424_2023_2804_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/c9f037277fa4/424_2023_2804_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/037ec5020741/424_2023_2804_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/02b777625f13/424_2023_2804_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/fc28a11f01dc/424_2023_2804_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/343868c3aded/424_2023_2804_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/c9f037277fa4/424_2023_2804_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/037ec5020741/424_2023_2804_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/02b777625f13/424_2023_2804_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/fc28a11f01dc/424_2023_2804_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ccc/10105677/343868c3aded/424_2023_2804_Fig5_HTML.jpg

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