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首页> 外文期刊>RSC Advances >Teneligliptin protects against ischemia/reperfusion-induced endothelial permeability in vivo and in vitro
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Teneligliptin protects against ischemia/reperfusion-induced endothelial permeability in vivo and in vitro

机译：Teneligliptin保护体内和体外缺血/再灌注诱导的内皮渗透性

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Ischemic stroke is a leading cause of disability and mortality worldwide, especially among the elderly population. Ischemia and reperfusion cause damage to cells and initiate an acute inflammatory response, which leads to cerebral endothelial dysfunction, increased endothelial permeability, and potentially permanent disability. Teneligliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor that has been used almost exclusively in the treatment of type 2 diabetes mellitus. However, it is still unknown whether teneligliptin possesses a protective effect in brain endothelial dysfunction in the context of ischemic stroke. In the present work, we demonstrate the potential of teneligliptin treatment to protect against ischemia/reperfusion-induced damage using a series of both in vivo and in vitro experiments. Our key findings are that administration of teneligliptin could reduce brain infarct volume, ameliorate neurological damage, and improve brain permeability by increasing the expression of the tight junction protein occludin in middle cerebral artery occlusion (MCAO) mice models. Importantly, teneligliptin displayed a robust protective effect against oxygen–glucose deprivation/reperfusion (OGD/R)-induced cell death of primary human brain microvascular endothelial cells (HBMVECs) in vitro . Notably, teneligliptin prevented OGD/R-induced increased endothelial monolayer permeability in HBMVECs by increasing the expression of occludin, which was mediated by the ERK5/KLF2 signaling pathway. These findings suggest that teneligliptin might serve as a potential therapeutic agent for the treatment of stroke.
机译：缺血性卒中是全世界残疾和死亡率的主要原因，特别是老年人。缺血和再灌注会对细胞造成损伤并引发急性炎症反应，这导致脑内皮功能障碍，增加内皮渗透性和潜在的永久性残疾。 Teneligliptin是二肽肽酶-4-4（DPP-4）抑制剂，其几乎完全用于治疗2型糖尿病。然而，仍然是缺血性卒中的背景下对脑内皮功能障碍的保护作用尚不清楚。在目前的工作中，我们证明了Teneligliptin治疗的潜力，用于使用体内和体外实验中的一系列方法来防止缺血/再灌注诱导的损伤。我们的主要研究结果是，Teneligliptin的给药可以降低脑梗塞体积，改善神经损伤，并通过增加中脑动脉闭塞（MCAO）小鼠模型中的紧密结蛋白闭塞蛋白的表达来改善脑渗透性。重要的是，Teneligliptin对氧葡萄糖剥夺/再灌注（OGD / R）诱导的致原性人脑微血管内皮细胞（HBMVECs）的细胞死亡造成鲁棒保护效果。值得注意的是，通过增加由ERK5 / KLF2信号传导途径介导的闭塞蛋白的表达，Teneligliptin预防OGD / R诱导的内皮单层渗透性增加了HBMVEC中的内皮单层渗透性。这些发现表明，Teneligliptin可以作为治疗中风的潜在治疗剂。

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