摘要
脑缺血再灌注后出现的胶质瘢痕,主要是由增殖的激活星形胶质细胞构成。研究证实胶质瘢痕不利于神经再生,由其构成的物理化学性屏障一方面会阻碍轴突再生,另一方面由激活星形胶质细胞产生的神经发育抑制因子也会阻碍中枢神经系统功能的恢复。研究表明内源性大麻素对星形胶质细胞增殖具有调控作用。为研究脑缺血再灌注损伤后外源性大麻素受体激动剂WIN55,212-2对胶质瘢痕的影响,本文使用大鼠中动脉闭塞模型,通过免疫组织化学法对样本中的激活星形胶质细胞标记物Vimentin、星形胶质细胞标记物GFAP、硫酸软骨素蛋白聚糖标记物Neurocan、以及Notch-1信号通路配体Jagged-1分子的表达进行检测。为研究药物的作用靶点,本文联合使用了大麻素Ⅰ型受体拮抗剂rimonabant。结果表明:WIN55,212-2在大麻素Ⅰ型受体的介导下,通过减少星形胶质细胞的增殖,显著降低激活星形胶质细胞上Jagged-1的表达水平,抑制了胶质瘢痕的形成。
Glial scar formation is a reactive cellular process mainly involving heavy proliferation of reactive astrocytes that occurs after cerebral ischemia-reperfusion injury.Notably,glial scar has been proven to have detrimental effects in neuroregeneration.One hand,the glial scar prevents axonal extensions via physical and chemical approaches,on the other hand,many neuro-developmental inhibitor molecules are secreted by the reactive astrocytes within the scar that prevent complete functional recovery of the central nervous system after cerebral ischemia-reperfusion injury.Endocannabinoids involve in the regulation of the proliferation of reactive astrocytes.To explore the effect of synthetic cannabinoid receptor agonist WIN55,212-2 on glial scar formation after cerebral ischemia-reperfusion injury,a middle cerebral artery occlusion（MCAO） model in adult rats was used in this study.The expression of Vimentin（markers for activated astrocytes）,GFAP（markers for astrocytes）,Neurocan（markers for chondroitin sulfate proteoglycan-3）,and Jagged-1（ligands for Notch-1 signaling pathway） were determinated by immunofluorescence staining.To determine potential drug target for WIN55,212-2,a specific inhibitor of cannabinoid receptor 1-rimonabant combine WIN55,212-2 treatment was also studied.The results showed that WIN55,212-2 significantly inhibited the glial scar formation through decreasing the reactive astrocytes proliferation,and the Jagged-1 expression in the reactive astrocytes via cannabinoid receptor 1.
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2013年第2期167-173,共7页
Journal of China Pharmaceutical University
基金
国家自然科学基金资助项目(No.81070967
No.81271338)
江苏省自然科学基金资助项目(No.BK2009296)
中国药科大学博士生拔尖人才培养资助项目(No.2011BPY05)~~
