摘要
目的研究白藜芦醇(resveratrol,Res)预处理对大鼠局灶性脑缺血/再灌注损伤后自噬的影响,探讨Res保护局灶性脑缺血/再灌注损伤的作用机制。方法将64只SD♂大鼠随机分成4组,假手术组(S组)、模型组(M组)、Res低剂量(15 mg.kg-1)干预组(R1组)和Res高剂量(40 mg.kg-1)干预组(R2组),用线栓法制备大鼠大脑中动脉栓塞(MCAO)模型,缺血2 h,再灌注24 h后,观察大鼠神经功能评分;透射电镜法观察神经元的超微结构及其内自噬空泡数量的变化;免疫组化法检测LC3的蛋白表达;RT-PCR法分别检测LC3和Beclin 1的mRNA表达。结果与M组相比,Res可明显减轻大鼠脑缺血/再灌注损伤的神经功能评分(P<0.05);使自噬泡数量明显增加;上调缺血皮质区脑组织LC3和Beclin 1蛋白及mRNA的表达(P<0.05)。结论 Res对大鼠局灶性脑缺血/再灌注损伤后神经元有保护作用,其机制可能与其诱导自噬的生成,上调LC3和Beclin 1的表达有关。
Aim To study the effect of resveratrol （Res） pretreatment on autophagy and expression of LC3 and Beclinl in rats following focal cerebral ische- mia-reperfusion injury, and explore the possible mech- anism of Res protection on focal cerebral ischemia- reperfusion injury. Methods Sixty-four male SD rats were randomly divided into four groups：sham operation group （S group）, model group （M group）, low dose of Res （15 mg kg-1） group （R1 group） and high dose of Res （40 mg kg-1） group （R2 group）. The middle cerebral artery occlusion （MCAO） for 2h was induced by intraluminal suture. After reperfusion for 24h, neurological scores were studied. The ultrastructure of neurone and the quantity changes of autophagic vacuoles were observed using transmission electron microscopy. The protein expression of LC3 was detected by immunohistochemistry; RT-PCR was used to ana- lyse the mRNA expression of LC3 and Beclin 1. Re- suits The neurological scores of rats treated with Res were reduced apparently compared with M group （P 〈 0.05）. Autophagic vacuoles increased after treatment with Res, and the protein and mRNA expression of LC3 and Beclin 1 in ischemia brain tissue were up-reg- ulated （ P 〈 0.05 ）. Conclusions Res could relieve the cerebral ischemia-reperfusion injury. The mecha- nisms could be related to the finding that Res induces increase of autophagy and up-regulates the expression of LC3 and Beclin 1.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2013年第7期995-998,共4页
Chinese Pharmacological Bulletin
基金
重庆市科技攻关计划项目(No CSTC
2008AB5118)
