摘要： 目的 探讨红系前体细胞（EPC）及其亚型在阿尔茨海默病中的作用及其机制。方法 对2018年10月至2019年10月在青海省人民医院首次诊断与治疗的30例阿尔茨海默病患者（AD组）予以奥氮平联合多奈哌齐治疗，同时选取相匹配的30例正常对照者（对照组），均采用流式细胞术检测外周血红系前体细胞及其亚型CD45⁺EPC和CD45^-EPC比例；进一步培养原代皮质神经元并构建阿尔茨海默病细胞模型，采用流式细胞术检测对照组、AD模型组、CD45⁺EPC组、CD45^-EPC组、Artemin阻断组神经元凋亡比例。结果 AD组与对照组、AD组治疗前后外周血红系前体细胞比例差异均无统计学意义（均P>0.05）；但AD组治疗前CD45⁺EPC比例（t=7.277，P=0.000）和活性氧含量（t=10.817，P=0.000）高于对照组、CD45^-EPC比例（t=7.277，P=0.000）和Artemin含量（t=6.547，P=0.000）低于对照组，而治疗前后CD45⁺EPC和CD45^-EPC比例、活性氧和Artemin含量差异均无统计学意义（均P>0.05）。神经元凋亡实验显示，不同处理组神经元凋亡比例差异有统计学意义（F=25.662，P=0.000），AD模型组（t=9.330，P=0.000）、CD45⁺EPC组（t=14.362，P=0.000）、CD45^-EPC组（t=2.423，P=0.036）和Artemin阻断组（t=9.970，P=0.000）神经元凋亡比例均高于对照组，AD模型组（t=4.548，P=0.001）、CD45⁺EPC组（t=8.759，P=0.000）和Artemin阻断组（t=5.387，P=0.000）均高于CD45^-EPC组，CD45⁺EPC组亦高于AD模型组（t=5.091，P=0.000）和Artemin阻断组（t=3.175，P=0.004）。结论 阿尔茨海默病患者外周血CD45⁺EPC比例显著增加，CD45^-EPC比例显著减少。CD45^-EPC可以通过分泌Artemin减少阿尔茨海默病引起的神经元凋亡。

关键词: 阿尔茨海默病, 红系前体细胞, 抗原,CD, 细胞凋亡

Abstract: Objective To investigate the role and mechanism of erythroid precursor cells (EPC) and its subtypes in Alzheimer's disease (AD).Methods The patients with AD (AD group) firstly diagnosed and treated in Qinghai Provincial People's Hospital from October 2018 to October 2019 were included, and olanzapine combined with donepezil were used for treatment; while 30 healthy volunteers were selected as the control group. The proportion of EPC, CD45⁺EPC and CD45^-EPC in peripheral blood in control group and AD group before and after treatment was detected and sorted by flow cytometry. Primary cortical neurons were used to construct AD cells model, flow cytometry was used to detect the apoptosis of neurons in control group, AD model group, CD45⁺EPC group, CD45^-EPC group and Artemin block group.Results There was no significant difference in the proportion of EPC in peripheral blood between AD group and control group, or between AD group before and after treatment (P>0.05, for all). However, the proportion of CD45⁺EPC subtype (t=7.277, P=0.000) and ROS content (t=10.817, P=0.000) in AD group before treatment were higher than those in control group. The proportion of CD45^-EPC subtype (t=7.277, P=0.000) and Artemin content (t=6.547, P=0.000) were lower than those in control group, but there were no significant differences in proportion of CD45⁺EPC and CD45^-EPC subtypes, ROS and Artemin contents before and after treatment in AD group (P>0.05, for all). Neuronal apoptosis experiment showed the proportion of neuronal apoptosis in different treatment groups was significantly different (F = 25.662, P=0.000). The proportion of neuronal apoptosis in AD model group (t=9.330, P=0.000), CD45⁺EPC group (t=14.362, P=0.000), CD45^-EPC group (t=2.423, P=0.036) and Artemin block group (t=9.970, P=0.000) were higher than those in control group. AD model group (t=4.548, P=0.001), CD45⁺EPC group (t=8.759, P=0.000), Artemin block group (t=5.387, P=0.000) were higher than those in CD45^-EPC group. CD45⁺EPC group was also higher than that in AD model group (t=5.091, P=0.000) and Artemin block group (t=3.175, P=0.004).Conclusions The proportion of CD45⁺EPC subtype in peripheral blood of AD patients was significantly increased and the proportion of CD45^-EPC subtype was decreased. CD45^-EPC subtype can reduce the neuronal apoptosis induced by AD by secreting Artemin.

Key words: Alzheimer disease, Erythroid precursor cells, Antigens, CD, apoptosis