柿叶黄酮类化合物对APP/PS1转基因小鼠脑组织突触的保护作用

Synapse-protective effect of flavonoids extracted from the leaves of Diospyros kaki in APP/PS1 transgenic mice

目的探讨柿叶黄酮类提取物(FLDK)对APP/PS1小鼠认知水平、突触结构及突触相关蛋白表达的影响。方法 20只4月龄APP/PS1小鼠,随机分为阿尔茨海默病(AD)模型组(AD组)及治疗组(AD+FLDK组),每组10只;10只4月龄C57BL/6小鼠为正常对照组(NC组)。AD+FLDK组给予FLDK 80 mg/(kg·d)灌胃干预60 d,AD组与NC组同样方法给予等量生理盐水60 d。分别采用M orris水迷宫测试小鼠逃避潜伏期(EL)及穿越平台次数,电镜观察突触超微结构,并用免疫组织化学方法检测皮层及海马区突触素(SYP)和大脑发育调节蛋白(drebrin)的含量。结果与NC组相比,AD组小鼠EL明显延长,穿越平台次数显著减少,突触结构模糊,SYP及drebrin表达明显减少。与AD组相比,AD+FLDK组EL减少,穿越平台次数明显增多,突触结构更完整且SYP、drebrin表达显著增加。结论 FLDK可显著改善APP/PS1小鼠学习记忆水平,增强突触结构完整性,提高突触相关蛋白含量,具有认知及突触保护作用。

Objective To investigate the effect of flavonoids extracted from the leaves of Diospyros kaki（ FLDK） on cognition levels,synapse structure and the expression of synapse-related proteins in APP / PS1 transgenic mouse.Methods Twenty APP / PS1 mice of four-month old were randomly divided into Alzheimers disease（ AD） model group（ AD group） and treatment group（ AD ＋ FLDK group）,ten in each group; ten C57 BL /6 mice of four-month old were regarded as normal control group（ NC group）. AD ＋ FLDK group was treated intragastrically with 80 mg /（ kg·d）FLDK,while AD and NC groups were fed intragastrically with the same volume of normal saline. Morris water maze was used to test the escape latency（ EL） and number of crossing,transmission electron microscope was used to observe the ultrastructure of synapse,and immunohistochemistry was used to detect the expression levels of synaptophysin and drebrin. Results Compared with NC group,the EL was prolonged,crossing numbers decreased,the synapse ultrastructure was damaged and synapse-related protein levels decreased in AD group. Compared with AD group,EL decreased and crossing number increased obviously,synapse ultrastructure was clearer and synapse-related protein levels increased in AD ＋ FLDK group. Conclusion FLDK can improve cognitive decline in APP / PS1 transgenic mouse,protect the integrity of synapse,and increase the synapse-related protein levels,thus can enhance cognition levels and protect synapse.