TREK-2 Mediates the Neuroprotective Effect of Isoflurane Preconditioning Against Acute Cerebral Ischemia in the Rat

作者：Guangchao Zhao, Lujia Yang, Shiquan Wang, Min Cai, Sisi Sun, Hailong Dong, Lize Xiong · 发表于：Rejuvenation Research · 年份：2018 · DOI：10.1089/rej.2017.2039 · 被引用次数：15 · 研究领域：Anesthesia and Neurotoxicity Research、Cardiac Ischemia and Reperfusion、Neuroinflammation and Neurodegeneration Mechanisms

It is known that preconditional treatment with volatile anesthetics can induce tolerance of the brain to stroke. A previous study demonstrated that the involvement of TREK-1, a two-pore domain K+ channel, in sevoflurane preconditioning induced neuroprotection against focal cerebral ischemia in rats. The present study testified whether TREK-2, another anesthetic-target K+ channel, is also associated with volatile anesthetic-induced neuroprotection, and further explored its potential mechanism. Rats preconditioned with isoflurane were subjected to 1.4vol% isoflurane plus 98% O 2 (1.5 L/min) inhalation for 1 hour daily and continuing for 5 consecutive days. Then, these rats were subjected to middle cerebral artery occlusion (MCAO) as focal cerebral ischemia model. The expression of TWIK-related K+ channel 2 (TREK-2) was analyzed by western blotting and quantitative real-time RT-PCR, and its downstream signaling molecules, protein kinase C (PKC) alpha, extracellular signal-regulated kinase 1/2 (ERK1/2), and pERK1/2 were detected by western blotting also. Subsequently, the expression of TREK-2 was regulated by siRNA transfection in the brain to clarify its role in the neuroprotection of isoflurane preconditioning. Neurological scores, infarction volume, and TdT-mediated dUTP Nick-End Labeling (TUNEL) staining were examined to evaluate the outcomes. The impact of TREK-2 on the expression of its downstream signaling molecules was also examined for preliminary analysis of the possibl...