摘要
Ischemia/reperfusion is known to greatly increase oxidative stress in the penumbra,which results in brain damage.Integrinαvβ3 is selectively up-regulated with ischemic injury to the brain and remains elevated throughout reperfusion.We determined whether or not a new compound biotinylated-LXW7-ceria nanoparticle(Ce NP)(b LXW7-Ce NP)plays a role in brain protection in the rat model of middle cerebral artery occlusion/reperfusion and shows better effects than Ce NPs alone in improving the outcomes of focal oxidative stress and apoptosis more effectively.Male Sprague-Dawley rats were subjected to focal cerebral ischemia for 2 h followed by a 24-h reperfusion.Drug treatment was intravenously administered via the caudal vein 1 h after occlusion.Rats were randomly divided into the following 4 groups:b LXW7-Ce NP treatment group(0.5 mg/kg);Ce NP treatment group(0.5 mg/kg);control saline group;and sham group.Brains were harvested 24 h after reperfusion,and the neurologic deficit scores,infarction volume,blood-brain barrier(BBB)disruption,and the level of oxidative stress and apoptosis were determined.Results showed that the b LXW7-Ce NP and Ce NP treatments could improve neurologic deficit scores,infarction volume,BBB disruption,and the level of oxidative stress and apoptosis.Compound b LXW7-Ce NP treatment exhibited better effects than Ce Np treatment and showed remarkable statistical differences in the infarction volume,the degree of BBB breakdown,the apoptosis and oxidative stress,apart from neurologic deficit scores.Thus,we concluded that b LXW7-Ce NP protects against acute cerebral ischemia/reperfusion injury.BLXW7,as a ligand of integrinαvβ3,may be able to effectively localize the anti-oxidant Ce NPs to the ischemic penumbra region,which may provide more adequate opportunities for Ce NPs to exert anti-oxidative stress effects and subsequently reduce apoptosis in acute cerebral ischemia/reperfusion.
作者
Ting ZHANG
Chang-yan LI
Jing-jing JIA
Jie-shan CHI
Da ZHOU
Jian-zhou LI
Xiao-ma LIU
Jun ZHANG
Li YI
张婷;李常艳;贾静静;池洁珊;周达;李鉴洲;刘小马;张军;易黎(Department of Neurology,Peking University Shenzhen Hospital,Shenzhen 518000,China;College of Chemistry and Chemical Engineering,Inner Mongolia University,Hohhot 010021,China;Department of Neurology,Xuanwu Hospital,Capital Medical University,Beijing 100053,China)
基金
supported by grants from Shenzhen Science and Technology Innovation Committee(No.JCYJ20140415162543033)
Startup Fund Project of Inner Mongolia University(No.21300-5145152)
Key Project of Education Department of Inner Mongolia(No.NJZZ16015)
the Natural Science Foundation of Inner Mongolia(No.2016MS0216)
