摘要
观察毛冬青甲素(ilexonin A,IA)对大鼠脑缺血再灌注后bFGF、GAP-43表达及神经元再生的影响,并探讨其神经保护的机制。通过建立大鼠大脑中动脉阻塞模型(MCAO),于脑缺血前及再灌注后给予腹腔注射IA(20和40 mg·kg-1)至3、7、14及28天(1次/天),以神经损伤严重程度评分(neurological severity scores,NSS)进行神经功能缺损评分,Nissl和TUNEL染色法观察不同时段缺血区周边组织神经元存活和凋亡情况,蛋白免疫印迹法和免疫荧光双标法检测bFGF、GAP-43的表达和神经元的再生。IA干预后,大鼠NSS评分较模型组明显减少(3天和7天),TUNEL阳性神经元减少(3天),Nissl阳性神经元增多(3天),治疗组各时段bFGF、GAP-43蛋白的表达水平明显增高,免疫荧光染色可见缺血周边区皮层有神经元再生,表现为Brdu/NeuN共表达;IA处理后Brdu/NeuN双阳性的细胞明显增加,以40 mg·kg-1剂量组最为显著。IA的神经保护机制可能与抑制缺血区周边组织神经元凋亡,促进bFGF、GAP-43的表达和神经元再生有关。
This study is to observe the effect of ilexonin A（IA） on the expression of basic fibroblast growth factor（bFGF） and growth associated protein-43（GAP-43）,and neurogenesis after cerebral ischemia-reperfusion in rats and explore its possible mechanism of protecting neuronal injury.Models of middle cerebral artery occlusion（MCAO） were established in SD rats.Before and after two hours ischemia-reperfusion,IA（20 and 40 mg·kg 1） was injected immediately and on 3,7,14,and 28 d once a day.The neurological severity was evaluated by neurological severity scores（NSS）;neuronal injury in the boundary zone of the infarction area was evaluated by TUNEL and Nissl staining.The expressions of bFGF and GAP-43 and neurogenesis were evaluated by Western blotting and 5-bromodeoxyuridine（Brdu） fluorescence staining,respectively.After treatment with IA,the NSS of treatment groups were lower than that of the models（3 and 7 d）.The number of TUNEL positive neurons decreased and Nissl positive neurons increased at the same time（3 d）.The expressions of bFGF and GAP-43 increased significantly in the boundary zone of the infarction area when compared to model group.Moreover,IA markedly enhanced the neurogenesis in the brain after ischemia-reperfusion,which revealed an increase of Brdu/NeuN positive cells in the boundary zone of the infarction area.The possible mechanism of protecting neuronal injury of IA may be related to inhibition on neuronal apoptosis,upregulation of bFGF and GAP-43,and neurogenesis in boundary zone of infarction after cerebral ischemia-reperfusion.
出处
《药学学报》
CAS
CSCD
北大核心
2011年第9期1065-1071,共7页
Acta Pharmaceutica Sinica
基金
福建省教育厅高等学校新世纪优秀人才支持项目(NCETFJ-0704)
福建医科大学教授学术发展基金(JS09014)
