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.

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. [ABSTRACT FROM AUTHOR]