| 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。 |
| 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 |
| DOI：10.11656/j.issn.1673-9043.2021.03.22 |
| 分类号:R285.5 |
| 基金项目:黑龙江省教育厅基本科研业务费基础研究项目（2017-KYYWF-0700）。 |
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| Effect of betulin on the expression of APH-1 and PEN-2 in hippocampal neurons of Alzheimer's model rats |
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JIN Yan, FU Zenghui, LIN Zaihong, JIANG Yan, LIU Jing, DU Shu, ZHANG Guangping, CHEN Tuantuan
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Department of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar 161002, China
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| Abstract: |
| [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 of γ-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. |
| Key words: betulin senile dementia SD rat APH-1 PEN-2 γ-secretase |
