Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.

Melatonin alleviates brain and peripheral tissue edema in a neonatal rat model of hypoxic-ischemic brain damage: the involvement of edema related proteins.
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褪黑素减轻缺氧缺血性脑损伤新生大鼠模型中的脑和周围组织水肿:水肿相关蛋白的参与

DOI:
10.1186/s12887-017-0824-x
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发表时间:
2017-03-28
期刊:
影响因子:
2.4
通讯作者:
Feng X
Feng X
中科院分区:
医学3区
文献类型:
--
作者:
Xu LX;Lv Y;Li YH;Ding X;Wang Y;Han X;Liu MH;Sun B;Feng X

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背景研究表明脑水肿可能参与了缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)的病理生理过程,褪黑素可能对脑损伤具有神经保护作用。然而,很少有人知道的机制,涉及褪黑激素在脑和周围组织的保护作用后,缺氧缺血性脑病。本研究旨在探讨褪黑素对新生大鼠缺氧缺血性脑损伤(hypoxic-ischemic brain damage,HIBD)模型多器官功能及水肿相关蛋白表达的影响。在HIBD或假损伤后,大鼠分别接受褪黑激素或等体积载体的腹腔注射。结果(1)H-E染色和透射电镜观察表明,褪黑素可减轻HIBD引起的脑和外周器官组织学损伤,并能减轻HIBD引起的脑和外周器官组织学损伤。(2)褪黑素可减轻HIBD引起的脑水肿,主要表现为脑含水量增加。(3)结论褪黑素对HIBD后脑组织及周围器官有保护作用,其对HIBD后脑水肿相关蛋白AQP-4、ZO-1、occludin的保护作用可能与其对HIBD后脑组织及周围器官的保护作用有关。可能间接参与了褪黑素的水肿保护机制。
BackgroundPrevious studies have indicated edema may be involved in the pathophysiology following hypoxic-ischemic encephalopathy (HIE), and melatonin may exhibit neuro-protection against brain insults. However, little is known regarding the mechanisms that involve the protective effects of melatonin in the brain and peripheral tissues after HIE. The present study aimed to examine the effects of melatonin on multiple organs, and the expression of edema related proteins in a neonatal rat model of hypoxic-ischemic brain damage (HIBD).MethodsOne hundred ninety-two neonatal rats were randomly divided into three subgroups that underwent a sham surgery or HIBD. After the HIBD or sham-injury, the rats received an intraperitoneal injection of melatonin or an equal volume vehicle, respectively. We investigated the effects of melatonin on brain, kidney, and colon edema via histological examination and the expression of edema related proteins, including AQP-4, ZO-1 and occludin, via qPCR and western blot.ResultsOur data indicated (1) Melatonin reduced the histological injury in the brain and peripheral organs induced by HIBD as assessed via H-E staining and transmission electron microscopy. (2) Melatonin alleviated the HIBD-induced cerebral edema characterized by increased brain water content. (3) HIBD induced significant changes of edema related proteins, such as AQP-4, ZO-1 and occludin, and these changes were partially reversed by melatonin treatment.ConclusionsThese findings provide substantial evidence that melatonin treatment has protective effects on the brain and peripheral organs after HIBD, and the edema related proteins, AQP4, ZO-1, and occludin, may indirectly contribute tothe mechanism of the edema protection by melatonin.