Iptakalim,an ATP-sensitive potassium channel opener,confers neuroprotection against cerebral ischemia/reperfusion injury in rats by protecting neurovascular unit cells  

作　　者：Yu-hua RAN Hai WAN 

机构地区：[1]Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Beijing 100850, China [2]Thadweik Academy of Medicine, Beijing 100039, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2011年第10期835-845,共11页浙江大学学报（英文版）B辑（生物医学与生物技术）

摘　　要：Objective:To investigate the role of iptakalim,an ATP-sensitive potassium channel opener,in transient cerebral ischemia/reperfusion (I/R) injury and its involved mechanisms.Methods:Intraluminal occlusion of middle cerebral artery (MCAO) in a rat model was used to investigate the effect of iptakalim at different time points.Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride,and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax.In vitro,neurovascular unit (NVU) cells,including rat primary cortical neurons,astrocytes,and cerebral microvascular endothelial cells,were cultured and underwent oxygen-glucose deprivation (OGD).The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments,which were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase.Caspase-3,Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction (PCR).Results:Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes,improved neurological scores,and attenuated brain edema after cerebral I/R injury.Iptakalim treatment (0 h after reperfusion) also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry.Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes,and lactate dehydrogenase release from cerebral microvascular endothelial cells.Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells.Conclusions:Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.Objective： To investigate the role of iptakalim, an ATP-sensitive potassium channel opener, in transient cerebral ischemia/reperfusion （I/R） injury and its involved mechanisms. Methods： Intraluminal occlusion of middle cerebral artery （MCAO） in a rat model was used to investigate the effect of iptakalim at different time points. Infarct volume was measured by staining with 2,3,5-triphenyltetrazolium chloride, and immunohistochemistry was used to evaluate the expressions of Bcl-2 and Bax. In vitro, neurovascular unit （NVU） cells, including rat primary cortical neurons, astrocytes, and cerebral microvascular endothelial cells, were cultured and underwent oxygen-glucose deprivation （OGD）. The protective effect of iptakalim on NVU cells was investigated by cell viability and injury assessments, which were measured by 3-（4,5-dimethylthiazol-2-yl）-2,5-diphenyltetrazolium bromide and release of lactate dehydrogenase. Caspase-3, Bcl-2 and Bax mRNA expressions were evaluated by real-time polymerase chain reaction （PCR）. Results： Administration of iptakalim 0 or 1 h after reperfusion significantly reduced infarct volumes, improved neurological scores, and attenuated brain edema after cerebral I/R injury. Iptakalim treatment （0 h after reperfusion） also reduced caspase-3 expression and increased the ratio of Bcl-2 to Bax by immunohistochemistry. Iptakalim inhibited OGD-induced cell death in cultured neurons and astrocytes, and lactate dehydrogenase release from cerebral microvascular endothelial cells. Iptakalim reduced mRNA expression of caspase-3 and increased the ratio of Bcl-2 to Bax in NVU cells. Conclusions： Iptakalim confers neuroprotection against cerebral I/R injury by protecting NVU cells via inhibiting of apoptosis.

关 键 词：Neurovascular unit Cerebral ischemia/reperfusion （I/R） injury ATP-sensitive potassium channel opener NEUROPROTECTION Apoptosis 

分 类 号：R96[医药卫生—药理学]