Sevoflurane postconditioning improves spatial learning and memory ability involving mitochondrial permeability transition pore in hemorrhagic shock and resuscitation rats

作者：Li Zhang, Li Huang, Jingxian Wang, Muchun Zhang, Ye Zhang, Xianwen Hu · 发表于：Brain and Behavior · 年份：2019 · DOI：10.1002/brb3.1501 · 被引用次数：15 · 研究领域：Cardiac Ischemia and Reperfusion、Anesthesia and Neurotoxicity Research、Intensive Care Unit Cognitive Disorders

BACKGROUND: Hemorrhagic shock induces the cognitive deficiency. Sevoflurane postconditioning has been documented to provide neuroprotection against ischemic-reperfusion injury by suppressing apoptosis. Mitochondrial permeability transition pore (mPTP) plays an important role in apoptosis, but it is unknown if the protective effect of sevoflurane postconditioning on hemorrhagic shock and resuscitation is associated with the change of mPTP opening. Hence, the aim of the study was to find out the precise mechanism of the sevoflurane postconditioning. METHODS: Sprague Dawley rats were subjected to hemorrhage shock for 60 min and then exposed to 2.4% sevoflurane for 30 min at the instant of reperfusion. Additionally, an opener (atractyloside) or an inhibitor (cyclosporine A) of mPTP was used in the animal model before sevoflurane postconditioning. Rats were randomly assigned into groups of Sham, Shock, Shock+Sevoflurane, Shock+Atractyloside, Shock+Sevoflurane+Atractyloside, Shock+Cyclosporin A, and Shock+Sevoflurane+Cyclosporin A treatment. Rat behavior was assessed for 5 days by Morris water maze 72 hr after surgery, and then hippocampus CA1 region was immunohistochemically stained. Brains were harvested 24 hr after surgery to detect the protein expression levels of Bcl-2, Bax, and cytochrome C by Western blot, the changes of mPTP opening, and mitochondrial membrane potential (MMP). RESULTS: We found that sevoflurane postconditioning significantly improved rats' spatial learning ...