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芹菜素介导Caveolin-1对脑缺血大鼠认知功能的改善作用
涂丰霞, 张惠梅, 谢庆凤, 庞琼怡, 陈翔
温州医科大学附属第二医院、育英儿童医院康复医学科
摘要:
目的探讨芹菜素对脑缺血大鼠认知功能的改善作用及潜在的分子机制。方法选择清洁级健康雄性SD大鼠32只,采用随机数字表法分为假手术组、模型组、低剂量芹菜素干预组(低芹菜素组)及高剂量芹菜素干预组(高芹菜素组),每组8只。采用线栓法制备大鼠大脑中动脉缺血再灌注模型,假手术组不阻断大脑中动脉。采用水迷宫来检测大鼠脑缺血后空间学习记忆功能,RT-qPCR法检测缺血侧海马小凹蛋白1(Caveolin-1)、N-甲基-D-天冬氨酸受体亚单位2B(NR2B)mRNA表达,采用Westernblot法检测缺血侧海马Caveolin-1蛋白表达,免疫组化法检测缺血侧海马NR2B表达部位及水平。结果模型组大鼠第26、27天逃避潜伏期均大于假手术组,差异均有统计学意义(t=2.138、3.001,均P<0.05)。高、低芹菜素组大鼠第27天逃避潜伏期均小于模型组,差异均有统计学意义(t=2.193、2.283,均P<0.05)。模型组大鼠空间探索时间小于假手术组,差异有统计学意义(t=2.789,P<0.01);高、低芹菜素组大鼠,空间探索时间均大于模型组,差异均有统计学意义(t=2.368、2.060,均P<0.05)。模型组Caveolin-1表达升高,高芹菜素组Caveolin-1mRNA和蛋白表达较模型组增加,差异均有统计学意义(t=2.321、2.553,P<0.05)。模型组NR2B表达减少,芹菜素干预能上调其表达(P<0.05)。结论芹菜素可通过促进Caveolin-1、NR2B表达,起到改善大鼠脑缺血后认知功能的作用。
关键词:  芹菜素 脑缺血 认知 小凹蛋白 1 N- 甲基 -D- 天冬氨酸受体亚单位 2B
DOI:10.12056/j.issn.1006-2785.2018.40.11.2018-112
分类号:
基金项目:浙江省医药卫生项目(2016KYB201);温州市科技局课题(Y20150017);温州医科大学附属第二医院重点建设学科
Apigenin improve cognitive function of rats after cerebral ischemic injury via Caveolin-1 pathway
the Second Affiliated Hospital of Wenzhou Medical University
Abstract:
Objective To examine the effect of apigenin on cognitive function of rats after cerebral ischemia and reperfusion injury and the related molecular mechanisms. Methods Thirty two SD rats were randomly divided into control group, model group, low-dose apigenin (20mg/kg) group) and high-dose apigenin (40mg/kg) group with 8 rats in each group. The cerebral ischemia/reperfusion model was established by thread embolization of middle cerebral artery and sham operation was performed in control group. Spatial learning and memory was assessed by Morris Water Maze; the mRNA expressions of Caveolin-1 and N-methyl-D-aspartate receptor 2B (NR2B) in rat hippocampus were detected by RT-qPCR after ischemia/reperfusion injury; the protein expression of Caveolin-1 in rat hippocampus was detected by Western Blot; the location and quantity of NR2B in rat hippocampus was observed by immnohitochemistry (IHC). Results Spatial learning and memory of model group were significantly impaired compared to control group assessed by morris water maze (P <0.01 or P <0.05). Apigenin treatment significantly ameliorated spatial learning and memory impairment of cerebral ischemic rats (P<0.05). The expression of Caveolin-1 was increased in rat hippocampus after cerebral ischemic injury, and apigenin upregulated the expression of Caveolin-1 (P<0.05). The expression of NR2B was decreased in rat hippocampus after cerebral ischemic injury, also, apigenin increased its expression (P<0.05). Conclusion This study suggest that apigenin can improve the cognitive func- tion of rats after cerebral ischemic injury, which is associated with upregulating the expression of Caveolin-1 and NR2B.
Key words:  Apigenin Cerebral ischemia Cognition Caveolin-1 N-methyl-D-aspartate receptor 2B