白桦脂醇对老年痴呆模型大鼠海马神经元APH-1及PEN-2表达的影响  

Effect of betulin on the expression of APH-1 and PEN-2 in hippocampal neurons of Alzheimer’s model rats

作　　者：金艳 傅增辉 林再红 姜岩 刘晶 杜姝 张广萍 陈团团 JIN Yan;FU Zenghui;LIN Zaihong;JIANG Yan;LIU Jing;DU Shu;ZHANG Guangping;CHEN Tuantuan(Department of Neurology,The Third Affiliated Hospital of Qiqihar Medical University,Qiqihar 161002,China)

机构地区：[1]齐齐哈尔医学院附属第三医院神经内科,齐齐哈尔161002

出　　处：《天津中医药大学学报》2021年第3期384-388,共5页Journal of Tianjin University of Traditional Chinese Medicine

基　　金：黑龙江省教育厅基本科研业务费基础研究项目(2017-KYYWF-0700)。

摘　　要：[目的]探讨白桦脂醇在老年痴呆大鼠中的干预作用及可能机制,为探索老年痴呆治疗提供新的可能。[方法]选用健康成年SD大鼠,随机分为对照组、模型组、白桦脂醇低剂量组和高剂量组,每组12只,连续灌胃给药3个月后进行相关指标检测,采用Morris水迷宫实验观测大鼠空间学习记忆能力,采用双荧光素酶报告基因系统检测γ分泌酶活性,采用实时定量-聚合酶链反应(RT-PCR)法和蛋白免疫印迹(Western Blot)法检测中前咽缺陷蛋白-1(APH-1)、缺氧诱导因子-1(HIF-1)、早老蛋白增强子-2(PEN-2)和环磷腺苷效应元件结合蛋白(CREB)表达水平。[结果]水迷宫检测结果发现白桦脂醇能明显改善模型大鼠认知功能障碍;双荧光素酶报告基因系统检测结果显示白桦脂醇可以抑制γ分泌酶活性;RT-PCR法和Western Blot法检测结果显示白桦脂醇可以抑制PEN-2和CREB表达,但对APH-1和HIF-1表达无明显影响。[结论]白桦脂醇可以显著改善老年痴呆模型大鼠的行为学,提高学习记忆能力和空间认知能力,显著降低老年痴呆模型大鼠PEN-2相关基因及蛋白的作用,但对APH-1相关基因及蛋白则无明显影响。[Objective]To investigate the intervening effect and possible mechanism of betulin in Alzheimer’s disease rats,so as to provide new possibilities for exploring the treatment of senile dementia.[Methods]Healthy adult SD rats were randomly divided into control group,model group,low-dose group and high-dose group.The 12 rats in each group were administrated by gavage continuously for 3 months,and the relevant indexes were detected by Morris water maze experiment.The activity ofγ-secretase was detected by double luciferase reporter gene system,the expression levels of APH-1,HIF-1,PEN-2 and CREB were detected by real-time PCR and western blotting.[Results]Water maze test showed that betulin ginseng can significantly improve the cognitive dysfunction in model rats;dual luciferase reporter system detection results showed that betulin can inhibit the gamma secretase activity;the detection result of real-time PCR and western blotting showed that betulin can inhibit PEN-2 and CREB expression,but no change in the expression of APH-1 and HIF-1.[Conclusion]Betulin can significantly improve AD model rats’s behavior of learning,memory ability and spatial cognitive ability.Betulin can inhibit the hippocampal CA1 region of PEN-2 related genes and proteins,but the APH-1 related gene and protein have no significant influence.

关 键 词：白桦脂醇 老年痴呆 SD大鼠 中前咽缺陷蛋白-1 早老蛋白增强子-2 Γ分泌酶 

分 类 号：R285.5[医药卫生—中药学]