Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran; Department of Physiology, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Physiology Research Center, Iran University of Medical Sciences, Tehran, Iran.
J Chem Neuroanat. 2021 Dec;118:102015. doi: 10.1016/j.jchemneu.2021.102015. Epub 2021 Aug 25.
Oxidative stress, an adverse consequence of brain ischemia-reperfusion injury (IRI), activates matrix metalloproteinase enzymes which cause to destruction of extracellular matrix and tight junction proteins. Oxidative stress during stroke increases serum endothelin-1 and endothelin B receptor (ETBR) expression. Apelin-13, an endogenous peptide, is expressed in numerous tissues that regulate diverse physiological and pathological processes. This study aimed to investigate the effect of intravenous (IV) injection of apelin-13 on cerebral vasogenic edema due to brain IRI. Animals were divided into sham, ischemia, and treat groups. IRI model was induced by middle cerebral artery occlusion (MCAO) for 60 min followed by 23 h reperfusion. Apelin-13 was injected into the tail vein 5 min before reperfusion. Neurological defects were evaluated with longa test. Brain water content and BBB permeability were assessed according to cerebral dry-wet weight and brain Evans blue extraction. Malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) were measured using the colorimetric method. Expression of occludin and claudin-5, matrix metalloproteinase- 2 and 9 (MMP-2 & 9) and, ETBR were evaluated using Western blot. Brain IRI was associated with BBB breakdowns and vasogenic edema. Apelin-13 significantly reduced BBB permeability and vasogenic edema. Apelin-13 significantly attenuated IRI-related oxidative stress. Apelin-13 decreased expression of mmp-2, 9 and ETBR, prevented from decrement of occludin and claudin-5 expersion, which protected BBB integrity and reduced vasogenic edema. In conclusion, our results have suggested that an IV injection of apelin-13 could somehow reduce vasogenic edema via targeting oxidative stress and ETBR expression.
氧化应激是脑缺血再灌注损伤（IRI）的一个不利后果，它会激活基质金属蛋白酶，导致细胞外基质和紧密连接蛋白的破坏。中风期间的氧化应激会增加血清内皮素-1 和内皮素 B 受体（ETBR）的表达。阿皮林-13 是一种内源性肽，在许多组织中表达，调节多种生理和病理过程。本研究旨在探讨静脉注射阿皮林-13 对脑 IRI 引起的血管源性脑水肿的影响。动物分为假手术、缺血和治疗组。通过大脑中动脉闭塞（MCAO）诱导 IRI 模型 60 分钟，然后再灌注 23 小时。阿皮林-13 在再灌注前 5 分钟经尾静脉注射。通过 longa 试验评估神经功能缺损。根据脑干湿重和脑 Evans 蓝提取评估脑水含量和 BBB 通透性。使用比色法测量丙二醛（MDA）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）。使用 Western blot 评估 occludin 和 claudin-5、基质金属蛋白酶-2 和 9（MMP-2 和 9）以及 ETBR 的表达。脑 IRI 与 BBB 破裂和血管源性脑水肿有关。阿皮林-13 显著降低 BBB 通透性和血管源性脑水肿。阿皮林-13 显著减轻 IRI 相关的氧化应激。阿皮林-13 降低了 mmp-2、9 和 ETBR 的表达，防止了 occludin 和 claudin-5 表达的减少，保护了 BBB 的完整性，减少了血管源性脑水肿。总之，我们的研究结果表明，静脉注射阿皮林-13 可能通过靶向氧化应激和 ETBR 表达来减轻血管源性脑水肿。
