| 王亚亚,赵 静,张玉明,朱丽娟,王 君.右美托咪啶通过抑制NADPH氧化酶2缓解氧化应激小鼠模型神经元的毒性和认知障碍的机制[J].现代生物医学进展英文版,2022,(4):637-641. |
| 右美托咪啶通过抑制NADPH氧化酶2缓解氧化应激小鼠模型神经元的毒性和认知障碍的机制 |
| DEXmedetomidine Alleviates the Toxicity and Cognitive Impairment of Oxidative Stress Mouse Model Neurons by Inhibiting NADPH Oxidase 2 |
| Received:July 04, 2021 Revised:July 27, 2021 |
| DOI：10.13241/j.cnki.pmb.2022.04.008 |
| 中文关键词: 右美托咪啶 NADPH氧化酶2 氧化应激 神经元 认知障碍 |
| 英文关键词: Dexmedetomidine NADPH oxidase 2 Oxidative stress Neurons Cognitive impairment |
| 基金项目:陕西省重点研发计划项目（2021SF-288） |
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| 中文摘要: |
| 摘要 目的：探讨右美托咪啶通过抑制NADPH氧化酶2缓解氧化应激小鼠模型神经元的毒性和认知障碍的机制。方法：10只野生型以及20只Sod1KO雄性BALB/c小鼠，12月龄，根据实验目的分为3组：对照组（野生型小鼠），模型组（氧化应激小鼠模型）和DEX组（氧化应激小鼠模型+50 μg/kg DEX治疗），每组10只。通过MWM 测试检测小鼠的空间学习和记忆能力。通过免疫染色检测海马中Neu-N+细胞数和PSD-95表达水平。通过蛋白质印迹检测海马中Neu-N、PSD-95、TH、总α-突触核蛋白和Ser129-磷酸化α-突触核蛋白表达水平。通过ROS、MDA和SOD检测试剂盒分别检测ROS、MDA和SOD水平。通过 ELISA试剂盒检测NOX2水平。通过RT-qPCR检测IL-1β、IL-6和TNF-α水平。结果：对照小鼠表现出正常的空间学习功能，与对照组小鼠相比，模型组小鼠逃避潜伏期和游泳距离增加（P<0.05），而DEX治疗能够降低模型组小鼠逃避潜伏期和游泳距离（P<0.05）。三组小鼠平均游泳速度没有统计性差异（P>0.05）。与对照组小鼠相比，模型组小鼠小鼠海马中Neu-N+细胞数和PSD-95表达水平降低（P<0.05），而DEX治疗能够增加小鼠海马中Neu-N+细胞数和PSD-95表达水平（P<0.05）。与对照组小鼠相比，模型组小鼠小鼠海马中Neu-N、PSD-95和TH蛋白表达水平降低（P<0.05），总α-突触核蛋白和Ser129-磷酸化α-突触核蛋白表达水平升高（P<0.05），而DEX治疗能够增加小鼠海马中Neu-N、PSD-95和TH蛋白表达水平（P<0.05），降低总α-突触核蛋白和Ser129-磷酸化α-突触核蛋白表达水平（P<0.05）。与对照组小鼠相比，模型组小鼠ROS和MDA水平增加，SOD水平降低（P<0.05），而DEX治疗能够降低ROS和MDA水平，增加SOD水平（P<0.05）。与对照组小鼠相比，模型组小鼠NOX2水平增加（P<0.05），而DEX治疗能够降低NOX2水平（P<0.05）。与对照组小鼠相比，模型组小鼠IL-1β、IL-6和TNF-α水平增加（P<0.05），而DEX治疗能够降低IL-1β、IL-6和TNF-α水平（P<0.05）。结论：DEX对NOX2的抑制可通过抑制小鼠模型中的氧化应激和神经炎症来阻断学习和记忆障碍以及海马神经变性。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the mechanism of DEXmedetomidine alleviating the toxicity and cognitive impairment of oxidative stress mouse model neurons by inhibiting NADPH oxidase 2. Methods: 10 wild-type and 20 Sod1KO male BALB/c mice, 12 months old, according to the purpose of the experiment, they were divided into 3 groups: control group (wild-type mice), model group (oxidative stress mouse model) and DEX group (oxidative stress mouse model + 50 μg/kg DEX treatment), each with 10 mice. The MWM test was used to test the spatial learning and memory abilities of mice. The number of Neu-N+ cells in the hippocampus and the expression level of PSD-95 were detected by immunostaining. The expression levels of Neu-N, PSD-95, TH, total α-synuclein and Ser129-phosphorylated α-synuclein in the hippocampus were detected by Western blot. ROS, MDA and SOD detection kits were used to detect ROS, MDA and SOD levels respectively. The NOX2 level was detected by ELISA kit. The levels of IL-1β, IL-6 and TNF-α were detected by RT-qPCR. Results: The control mice showed normal spatial learning function. Compared with the control mice, the escape latency and swimming distance of the model group increased (P<0.05), while DEX treatment could reduce the escape latency and swimming distance of the model group. Distance (P<0.05). There was no statistical difference in the average swimming speed of the three groups of mice (P>0.05). Compared with control mice, the number of Neu-N+ cells and PSD-95 expression in the hippocampus of the model group decreased (P<0.05), while DEX treatment can increase the number of Neu-N+ cells and PSD in the hippocampus of mice -95 expression level (P<0.05). Compared with the control mice, the expression levels of Neu-N, PSD-95 and TH protein in the hippocampus of the model group mice decreased (P<0.05), and the total α-synuclein and Ser129-phosphorylated α-synonym The expression level of nucleoprotein increased (P<0.05), and DEX treatment can increase the expression level of Neu-N, PSD-95 and TH protein in the hippocampus of mice (P<0.05), and reduce the total α-synuclein and Ser129 -Phosphorylated α-synuclein expression level (P<0.05). Compared with mice in the control group, the level of ROS and MDA in the model group increased, and the level of SOD decreased (P<0.05), while DEX treatment could reduce the level of ROS and MDA, and increase the level of SOD (P<0.05). Compared with the control group, the NOX2 level of the model group increased (P<0.05), and DEX treatment can reduce the NOX2 level (P<0.05). Compared with the control group, the level of IL-1β, IL-6 and TNF-α in the model group increased (P<0.05), and DEX treatment can reduce IL-1β, IL-6 and TNF-α level (P<0.05). Conclusion: The inhibition of NOX2 by DEX can block learning and memory impairment and hippocampal neurodegeneration by inhibiting oxidative stress and neuroinflammation in the mouse model. |
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