Mohaddes Gisou, Abdolalizadeh Jalal, Babri Shirin, Hossienzadeh Fezzeh
Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Exp Physiol. 2017 Mar 1;102(3):376-382. doi: 10.1113/EP086068.
What is the central question of this study? Is an anti-oedematous effect of ghrelin associated with increased expression of tight junction proteins in the hypoxic brain? What is the main finding and its importance? We showed that injection of ghrelin during acute and chronic systemic hypoxia is associated with increased expression of tight junction proteins and protection of the blood-brain barrier. Ghrelin appears to be a new therapeutic strategy for protection of the blood-brain barrier from disruption and prevention of brain oedema in hypoxic conditions. The blood-brain barrier, which serves to protect the homeostasis of the CNS, is formed by tight junction proteins. Several studies have indicated that systemic hypoxia leads to cerebral oedema through disruption of tight junction proteins, such as occludin and zonula occludens-1 (ZO-1). According to our previous studies, ghrelin attenuates cerebral oedema in the hypoxic brain. However, the mechanism is not completely understood. The present study was designed to determine the effect of ghrelin on occludin and ZO-1 in the hypoxic brain. Adult male Wistar rats were divided into acute and chronic control, acute or chronic hypoxia, and ghrelin-treated acute or chronic hypoxia groups. Hypoxic groups were kept in a hypoxic chamber (10-11% O ) for 2 (acute) or 10 days (chronic). Effects of ghrelin on occludin and ZO-1 protein levels were assessed using Western blotting. Western blot analysis revealed that the protein expression of ZO-1 and occludin decreased significantly in acute and chronic hypoxia. Ghrelin significantly increased ZO-1 protein expression in both acute and chronic hypoxia (P < 0.05). Ghrelin also increased occludin protein expression in chronic hypoxia (P < 0.05) but did not effectively change it in acute hypoxia. Our data showed that ghrelin injection maintains occludin and ZO-1 tight junction proteins, which may improve the integrity of the blood-brain barrier in hypoxic conditions.
本研究的核心问题是什么？胃饥饿素的抗水肿作用是否与缺氧脑紧密连接蛋白表达增加有关？主要发现及其重要性是什么？我们发现，在急性和慢性全身缺氧期间注射胃饥饿素与紧密连接蛋白表达增加及血脑屏障的保护有关。胃饥饿素似乎是一种新的治疗策略，可保护血脑屏障免受破坏，并预防缺氧条件下的脑水肿。血脑屏障由紧密连接蛋白形成，用于保护中枢神经系统的内环境稳定。多项研究表明，全身缺氧通过破坏紧密连接蛋白（如闭合蛋白和闭合小带蛋白1（ZO-1））导致脑水肿。根据我们之前的研究，胃饥饿素可减轻缺氧脑的脑水肿。然而，其机制尚未完全明确。本研究旨在确定胃饥饿素对缺氧脑闭合蛋白和ZO-1的影响。成年雄性Wistar大鼠分为急性和慢性对照组、急性或慢性缺氧组以及胃饥饿素治疗的急性或慢性缺氧组。缺氧组置于缺氧舱（氧含量10 - 11%）中2天（急性）或10天（慢性）。使用蛋白质印迹法评估胃饥饿素对闭合蛋白和ZO-1蛋白水平的影响。蛋白质印迹分析显示，急性和慢性缺氧时ZO-1和闭合蛋白的蛋白表达显著降低。胃饥饿素在急性和慢性缺氧时均显著增加ZO-1蛋白表达（P < 0.05）。胃饥饿素在慢性缺氧时也增加了闭合蛋白的蛋白表达（P < 0.05），但在急性缺氧时未有效改变其表达。我们的数据表明，注射胃饥饿素可维持闭合蛋白和ZO-1紧密连接蛋白，这可能改善缺氧条件下血脑屏障的完整性。
