| 引用本文: |
王南卜,王志芳,韩玉凤,康健,方永奇,李翎.β-细辛醚激活PINK1/Parkin介导的线粒体自噬改善APP/PS1小鼠认知和记忆功能障碍的研究[J].湖南中医药大学学报,2021,41(8):1178-1187[点击复制] |
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| β-细辛醚激活PINK1/Parkin介导的线粒体自噬改善APP/PS1小鼠认知和记忆功能障碍的研究 |
| 王南卜,王志芳,韩玉凤,康健,方永奇,李翎 |
| (广州中医药大学第一附属医院, 广东 广州 510006;广州中医药大学, 广东 广州 510006) |
| 摘要: |
| 目的 探讨β-细辛醚对淀粉样前体蛋白（APP）/早老素1（PS1）小鼠的作用机制及对PINK1/Parkin介导的线粒体自噬的影响。方法 将APP/PS1小鼠随机分为模型组、β-细辛醚低、中、高剂量组（15、30、45 mg/kg）、多奈哌齐组（1 mg/kg）、雷帕霉素组（4 mg/kg）、3-甲基腺嘌呤（3-MA）组（4 mg/kg）、环孢霉素A组（10 mg/kg），另设正常组，每组10只。各组灌胃给药，模型组和正常组用等体积蒸馏水代替，1次/d，给药30 d。观察各组小鼠水迷宫实验，蛋白质印迹法检测小鼠海马中APP、PS1、神经突触素1（SYN1）、β-位点淀粉样前体蛋白裂解酶1（BACE1）、LC3 I/II、Beclin-1、p62、PINK1、Parkin和p-Parkin蛋白表达水平；反转录聚合酶链反应检测APP、PS1、BACE1、LC3B、Beclin-1、p62和Parkin mRNA表达水平。结果 与模型组相比，β-细辛醚高剂量组、β-细辛醚中剂量组和多奈哌齐组APP/PS1小鼠的逃避潜伏期缩短（P<0.05或P<0.01），小鼠海马内APP、PS1、BACE1的表达下降（P<0.01），SYN1表达上升（P<0.05或P<0.01）；与模型组相比，β-细辛醚中剂量组APP/PS1小鼠内Beclin-1、LC3B表达均升高（P<0.05或P<0.01），p62表达下降（P<0.05）；与模型组相比，雷帕霉素组Beclin-1、LC3B表达均升高（P<0.05或P<0.01），p62表达下降（P<0.01）；与模型组相比，3-MA组p62表达升高（P<0.05）；与模型组相比，β-细辛醚中剂量组APP/PS1小鼠内PINK1、p-Parkin表达均显著升高（P<0.01）。结论 β-细辛醚通过激活PINK1-Parkin介导的线粒体自噬而影响阿尔茨海默病病理，这为应用β-细辛醚治疗阿尔茨海默病提供了新的靶点。 |
| 关键词: 阿尔茨海默病 β-细辛醚 线粒体自噬 PINK1 Parkin 淀粉样前体蛋白 早老素1 神经突触素1 |
| DOI：10.3969/j.issn.1674-070X.2021.08.008 |
| 投稿时间：2021-06-01 |
| 基金项目:国家自然科学基金项目（81903971）；广东省基础与应用基础研究基金项目（2021A1515011470）；广东省中医药信息化重点实验室项目（2021B1212040007）。 |
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| β-Asarone Improves Cognitive and Memory Impairment in APP/PS1 Mice by Activating PINK1/Parkin Mediated Mitochondrial Autophagy |
| WANG Nanbu,WANG Zhifang,HAN Yufeng,KANG Jian,FANG Yongqi,LI Ling |
| (The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, China;Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China) |
| Abstract: |
| Objective To explore the mechanism of β-asarone on APP/PS1 mice and its effect on the mitochondrial autophagy mediated by PINK1/Parkin. Methods APP/PS1 mice were randomly divided into model group, low/medium/high dose groups (15, 30, 45 mg/kg) of β-asarone, donepezil group (1 mg/kg), rapamycin group (4 mg/kg), 3-methyladenine (3-MA) group (4 mg/kg), cyclosporine A (CsA) group (10 mg/kg) and normal group, with 10 mice in each group. Each group was given intragastric administration, and model group and normal group were given equal volume distilled water once a day for 30 days. Water maze test was observed in each group. Amyloid precursor protein (APP), prosenoxin 1 (PS1), synaptophysin 1 (SYN1), β-site amyloid precursor protein lyase 1 (BACE1) and LC3I/II, Beclin-1, p62, PINK1, Parkin and p-Parkin were detected in the hippocampus of mice by western blot. The mRNA expression levels of APP, PS1, BACE1, LC3B, Beclin-1, P62 and Parkin were detected by reverse transcription polymerase chain reaction. Results Compared with the model group, the escape latency of APP/PS1 mice in β-asarone high dose group, β-asarone medium dose group and donepezil group was significantly shortened (P<0.05 or P<0.01), the expression of APP, PS1 and BACE1 in hippocampus of mice decreased (P<0.01), and the expression of SYN1 increased (P<0.05 or P<0.01); compared with the model group, the expression of Beclin-1 and LC3B in β-asarone medium dose group increased (P<0.01 or P<0.05), and the expression of p62 decreased (P<0.05); compared with the model group, the expression of Beclin-1 and LC3B in rapamycin group increased (P<0.05 or P<0.01), and the expression of p62 decreased (P<0.01); the expression of p62 in 3-MA group was higher than that model group (P<0.05); compared with the model group, the expression levels of PINK1 and p-Parkin in APP/PS1 mice in β-asarone medium dose group were significantly increased (P<0.01). Conclusion β-asarone may affect Alzheimer's Disease (AD) pathology by activating mitochondrial autophagy mediated by PINK1-Parkin, which provides a new target for the treatment of AD with β-asarone. |
| Key words: Alzheimer's disease β-asarone mitochondrial autophagy PINK1 Parkin amyloid precursor protein prosenoxin 1 synaptophysin 1 |
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