| 摘要: |
| 目的 初步探索乙酸盐（Ace）对1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导亚急性帕金森病小鼠的神经保护作用及可能机制。方法 将24只小鼠随机分为对照组、MPTP组、MPTP+Ace组，每组8只，对照组和MPTP组饮用正常饮用水，MPTP+Ace组饮用水中添加1 mol/L Ace，连续7 d后，MPTP组和MPTP+Ace组腹腔注射30 mg/kg MPTP连续7 d诱导亚急性帕金森病模型。采用震颤麻痹评分、爬杆实验、水迷宫实验检测小鼠的运动功能和认知功能，免疫组织化学染色检测小鼠海马组织小胶质细胞活化情况，ELISA检测小鼠外周血和海马组织促炎细胞因子的表达，蛋白质印迹法检测小鼠海马组织NF-κB/MAPK炎症信号通路蛋白p38和p65的表达。结果 与对照组相比，MPTP组小鼠震颤麻痹评分增高（P<0.05），爬杆时间延长（P<0.01），目标象限停留时间百分比、路程百分比及穿台次数减少（P均<0.01）；与MPTP组相比，MPTP+Ace组小鼠震颤麻痹评分降低（P<0.05），爬杆时间缩短（P<0.01），目标象限停留时间百分比、路程百分比及穿台次数增加（P均<0.01）。与对照组相比，MPTP组小鼠海马组织活化小胶质细胞增多，血清和海马组织促炎因子TNF-α和IL-6的表达水平升高（P均<0.01），海马组织磷酸化p38和磷酸化p65蛋白表达水平增高（P均<0.01）；与MPTP组相比，MPTP+Ace组小鼠海马组织活化小胶质细胞减少，血清和海马组织促炎因子TNF-α和IL-6的表达水平降低（P均<0.05），海马组织磷酸化p38和磷酸化p65蛋白表达水平降低（P均<0.01）。结论 Ace可通过抑制NF-κB/MAPK炎症信号通路减轻海马组织小胶质细胞活化，抑制中枢神经炎症反应，改善MPTP诱导帕金森病模型小鼠的运动和认知功能障碍。 |
| 关键词: 乙酸盐类 帕金森病 神经炎症 小神经胶质细胞 核因子κB p38丝裂原活化蛋白激酶类 |
| DOI：10.16781/j.CN31-2187/R.20211312 |
| 投稿时间：2021-12-28修订日期：2022-01-24 |
| 基金项目:国家自然科学基金（81701062），海军军医大学（第二军医大学）第一附属医院临床学科创新项目（2020YXK013）. |
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| Neuroprotective effect of acetate pretreatment on mouse model of MPTP-induced subacute Parkinson disease |
| YANG Wen-yu1,2,HUANG Jie2,CHANG Xin-ning2,YU Xi-ya2*,DENG Xiao-ming2* |
(1. School of Anesthesiology, Weifang Medical University, Weifang 261053, Shandong, China;
2. Department of Anesthesiology, The First Affiliated Hospital of Naval Medical University(Second Military Medical University), Shanghai 200433, China
*Corresponding authors) |
| Abstract: |
| Objective To preliminarily explore the neuroprotective effect of acetate (Ace) on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson disease mice and its mechanism. Methods Twenty-four mice were randomly divided into control group, MPTP group and MPTP+Ace group (8 mice in each group). The mice in the control group and MPTP group drank normal drinking water, and those in the MPTP+Ace group drank water containing 1 mol/L Ace. After 7 d, 30 mg/kg MPTP was injected intraperitoneally into the mice in the MPTP group and MPTP+Ace group to induce Parkinson disease model for 7 d. The motor function and cognitive function of mice were detected by tremor paralysis score, pole climbing test and Morris water maze, the activation of microglia in mouse hippocampus was detected by immunohistochemistry, the expression of proinflammatory cytokines in the peripheral blood and hippocampus was detected by enzyme-linked immunosorbent assay (ELISA), and the protein expression of p38 and p65 of nuclear factor κB (NF-κB)/mitogen-activated protein kinase (MAPK) pathway in the hippocampus was detected by Western blotting. Results Compared with the control group, the tremor paralysis score of the MPTP group was higher (P<0.05), the pole climbing time was longer (P<0.01), and the percentage of stay time in the target quadrant, the percentage of distance and the times of crossing the platform were decreased (all P<0.01). Compared with the MPTP group, the tremor paralysis score of the MPTP+ace group was lower (P<0.05), the pole climbing time was shorter (P<0.01), and the percentage of stay time in the target quadrant, the percentage of distance and the times of crossing the platform were increased (all P<0.01). Compared with the control group, the activated microglia in hippocampus of mice in the MPTP group were increased, the expression levels of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the serum and hippocampus were increased (all P<0.01), and the expression levels of phosphorylated p38 and phosphorylated p65 proteins in the hippocampus were increased (both P<0.01). Compared with the MPTP group, the activated microglia in the hippocampus of mice in the MPTP+Ace group were decreased, the expression levels of TNF-α and IL-6 in the serum and hippocampus were decreased (all P<0.05), and the expression levels of phosphorylated p38 and phosphorylated p65 in hippocampus were decreased (both P<0.01). Conclusion Ace can reduce microglia activation in the hippocampus by inhibiting NF-κB/MAPK inflammatory signaling pathway, inhibit the inflammatory response of central nervous system, and improve motor function and cognitive function of MPTP-induced Parkinson disease mice. |
| Key words: acetates Parkinson disease neuroinflammation microglia nuclear factor κB p38 mitogen-activated protein kinases |
