中国临床药理学杂志2024，Vol.40Issue(16)：2334-2338,5.DOI:10.13699/j.cnki.1001-6821.2024.16.007
Nptx2在阿尔茨海默病中通过抑制补体系统逆转小胶质细胞诱发突触损失的研究
Nptx2 reverses microglia-induced synaptic loss by inhibiting the complement system in Alzheimer's disease
摘要
Abstract
Objective To investigate the effects of neuronal pentraxin 2(Nptx2)on complement system,microglia activation and synaptic density in mice with Alzheimer's disease(AD).Methods Six-months-old APPswe/PS1dE9 double transgenic mice were divided into model group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and model+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 × 1010 GC),6-months-old wild-type mice were divided into control group(intracerebroventricularly injected with AAV-Veh 1 × 1010 GC)and control+AAV-Nptx2 group(intracerebroventricularly injected with AAV-Nptx2 1 x 1010 GC),with 12 mice in each group.One month later,the cognitive function of mice in each group was evaluated by Morris Water Maze test.The expression levels of Nptx2 and Iba1 proteins were measured by Western blot,the contents of complement related proteins were measured by enzyme linked immunosorbent assay,and the synaptic plasticity was evaluated by Golgi staining.Results The resident time in the platform quadrant of control,control+AAV-Nptx2,model and model+AAV-Nptx2 groups were(44.72±10.92),(53.32±10.29),(21.92±3.80)and(36.47±6.41)s;the number of crossing the platform were 10.08±2.64,9.58±3.09,2.25±1.29 and 5.92±1.38;the relative expression levels of Nptx2 protein were 0.33±0.06,0.63±0.10,0.09±0.03 and 0.57±0.22;the relative expression levels of Iba1 protein were 0.17±0.06,0.23±0.08,0.97±0.16 and 0.40±0.14;the synaptic densities were 22.75±4.27,29.25±4.78,8.25±2.99 and 23.75±4.86.Compared with the model group,the differences of above indexes in the model+AAV-Nptx2 and control groups were statistically significant(all P＜0.05).Conclusion Overexpression of Nptx2 protein can inhibit the activation of complement system,reduce the activation of microglia,and increase the synaptic density to alleviate cognitive impairment in AD mice.关键词
神经元正五聚蛋白Ⅱ/阿尔茨海默病/补体系统/小胶质细胞/突触Key words
recombinant neuronal pentraxin Ⅱ/Alzheimer's disease/complement system/microglia/synapses分类
医药卫生引用本文复制引用
谭辰熙,刘洋,邸辞寒,许德超,张会怡..Nptx2在阿尔茨海默病中通过抑制补体系统逆转小胶质细胞诱发突触损失的研究[J].中国临床药理学杂志,2024,40(16):2334-2338,5.基金项目
齐齐哈尔市科技计划联合引导基金资助项目(LHYD-202056) （LHYD-202056）
