论文部分内容阅读
目的:研究番荔枝酰胺衍生物FLZ对衰老小鼠学习记忆功能障碍的改善作用及相关机制。方法:24月龄自然衰老小鼠分别灌胃FLZ 75,150 mg.kg-1,qd,连续30 d。水迷宫检测小鼠学习记忆能力;Western blot检测相关蛋白的表达。结果:水迷宫结果显示,FLZ 150 mg.kg-1能明显改善自然衰老小鼠学习记忆功能。Western blot检测发现,FLZ 150 mg.kg-1可明显降低衰老小鼠海马β-淀粉样蛋白(β-amyloid,Aβ)、β-淀粉样前体蛋白裂解酶1(β-site amyloid precursor protein cleaving enzyme 1,BACE1)、淀粉样前体蛋白(amyloid protein precursor,APP)和早老素1(presenilin 1,PS1)-羧基端(COOH-terminal fragment,CTF)的表达,但对APP和PS1的表达没有明显影响。FLZ 150 mg.kg-1可明显提高衰老小鼠海马脑源性神经营养因子(brain-derived neurotrophin factor,BDNF)及受体酪氨酸激酶受体B(tyrosine kinase receptor,TrkB)的表达,同时能提高酪氨酸激酶(tyrosine kinase,TrkA)和降低神经营养因子低亲和力受体(p75NTR)的表达。而FLZ75 mg.kg-1对上述指标没有明显的改善作用。结论:FLZ具有抗脑衰老的作用,其作用机制与降低海马Aβ的沉积,提高神经营养因子BDNF的表达有关。
OBJECTIVE: To study the effect and mechanism of spinosad derivative FLZ on learning and memory dysfunction in senile mice. Methods: 24-month old aged mice were intragastrically administered with FLZ 75,150 mg.kg-1, qd for 30 days. Water maze test mice learning and memory ability; Western blot detection of related protein expression. Results: The water maze results show that FLZ 150 mg.kg-1 can significantly improve the learning and memory of mice with natural aging. Western blot showed that FLZ 150 mg.kg-1 could significantly reduce the β-site amyloid precursor protein cleaving (β-amyloid, Aβ), β-amyloid precursor protein cleaving enzyme 1, BACE1, amyloid protein precursor (APP) and presenilin 1 (PS1) -cold terminal (CTF), but not the expression of APP and PS1 Clearly affected. FLZ 150 mg.kg-1 could significantly increase the expression of brain-derived neurotrophin factor (BDNF) and tyrosine kinase receptor (TrkB) Can increase tyrosine kinase (tyrosine kinase, TrkA) and reduce the expression of neurotrophin low affinity receptor (p75NTR). The FLZ75 mg.kg-1 on the above indicators did not significantly improve the role. CONCLUSION: FLZ has anti-brain aging effect and its mechanism is related to the decrease of the deposition of Aβ in hippocampus and the increase of the expression of neurotrophic factor BDNF.