EPA对创伤性脑损伤APP/PS1转基因小鼠淀粉样肽沉积和认知功能的作用

EPA decreases the traumatic brain injury-induced amyloid deposition and improves the cognitive function in APP/PS1 transgenic mouse

目的探究二十碳五烯酸(EPA)对创伤性脑损伤APP/PS1转基因小鼠淀粉样肽沉积和认知功能障碍的作用。方法对3月龄APP/PS1小鼠施行创伤性脑损伤(TBI)手术并在手术当天即开始对其进行为期30天的EPA乙酯治疗(腹腔注射,1g/Kg/d)。TBI手术30天后(小鼠4月龄),通过HE染色和免疫组织化学检测小鼠脑内淀粉样肽(Aβ)负荷,通过Y-迷宫自发变更试验和高架十字迷宫试验检测小鼠认知功能状态。结果 TBI手术造成小鼠皮层明显空洞形成和组织缺损,4月龄APP/PS1/小鼠海马区开始出现Aβ斑块,TBI可显著加重APP/PS1小鼠海马区Aβ负荷,而EPA治疗后APP/PS1小鼠海马区Aβ负荷可恢复至生理水平。4月龄APP/PS1小鼠并未出现显著认知功能损害,TBI可使APP/PS1小鼠探索活跃度、空间工作记忆和危险识别能力明显降低,EPA治疗可恢复至未损伤小鼠同等水平。结论EPA治疗可降低创伤性脑损伤AD模型小鼠脑内淀粉样斑块沉积和改善认知功能障碍。

Objective To investigate the therapeutic effect of eicosapentenoic acid（EPA） on the traumatic brain injury-induced amyloid deposition and cognitive disorder in APP/PS1 transgenic mice.Methods The traumatic brain injury（TBI） surgery was performed on 3-month old APP/PS1 mice treated with EPA ethyl ester for 30 d（intravenous injection,1g/Kg/d） after surgery.The thirty days after TBI surgery（when mice were 4-month old）,intracerebral β-amyloid peptide burden was evaluated by HE staining and immunohistochemical staining,and cognition function was assessed by Ymaze spontaneous alteration test and elevated plus maze test.Results TBI surgery resulted in evident cavitation and tissue loss in the murine cortex,Aβ plaques were found in the hippocampus of 4-month old APP/PS1 mouse,while TBI significantly increased the Aβ burden in the hippocampus of APP/PS1 mouse,but restored to the almost physiological level after EPA treatment.Although 4-month old APP/PS1 mouse did not show obvious cognitive impairment,the exploration activity and spatial working memory and danger recognition in APP/PS1 mouse were dramatically damaged by TBI,but recovered to almost normal level by EPA treatment.Conclusion EPA treatment decreases the intracerebral amyloid deposition and improves the cognitive function in TBIinduced APP/PS1 transgenic mouse.