OBJECTIVE: This study aims to explore the role of rhynchophylline in middle cerebral artery occlusion (MCAO) induced ischemic stroke model and the potential mechanisms.
METHODS: Mice were randomly divided into the following three groups: Sham, MCAO + ddH2O, and MCAO + Rhy(40 mg/kg by oral gavage) groups. Cerebral ischemia was induced by MCAO. Cerebral blood flow was monitored to indicate the success of the ischemic model. The neurological severity score and a series of related behavior tests were performed(after MCAO 3d,7d,14d,21d,28d). Golgi staining and Sholl analysis were used to evaluate the complexity of dendrites and the density of dendritic spines. Immunohistochemistry was used to detect the expression of synapsin I and NeuN.
RESULTS: Administration of rhynchophylline for 7 consecutive days after the onset of cerebral ischemia alleviated the sensory-motor functional defects and ameliorated hippocampus-dependent spatial memory injury as well as reduced the infarct volume induced by MCAO. However, golgi staining and sholl analysis showed that rhynchophylline improved dendritic complexity and spine density as well as the synaptic plasticity. Furthermore,the expression of synapsin I and Neun was significantly reduced after cerebral ischemia and rhynchophylline administration ameliorated the loss of synapsin I.
CONCLUSIONS: Rhynchophylline is a promising treatment for ischemic stroke via improving synaptic plasticity and ameliorating the sensory-motor function.
目的:本研究旨在探讨钩藤碱在大脑中动脉闭塞(MCAO)诱导的缺血性脑卒中模型中的作用及可能的机制。
方法:小鼠随机分为以下三组:假,MCAO+ddH2O,和MCAO+Rhy(口服灌胃40mg/kg)组。MCAO诱发脑缺血。监测脑血流量以指示缺血模型的成功。进行了神经系统严重程度评分和一系列相关行为测试(在MCAO3d之后,7d,14d,21d,28d).高尔基染色和Sholl分析用于评估树突的复杂性和树突棘的密度。免疫组化法检测突触素I和NeuN的表达。
结果:脑缺血发作后连续7天给予钩藤碱减轻了感觉运动功能缺陷,改善了海马依赖性空间记忆损伤,并减少了由MCAO引起的梗死体积。然而,高尔基染色和sholl分析表明,钩藤碱改善了树突的复杂性和脊柱密度以及突触可塑性。此外,脑缺血后,突触素I和Neun的表达显着降低,钩藤碱可改善突触素I的丢失。
结论:钩藤碱通过改善突触可塑性和改善感觉-运动功能,是治疗缺血性中风的有希望的治疗方法。