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目的:探究肌萎缩性侧索硬化症(amyotrophic lateral sclerosis，ALS)患者血清外泌体和外周血CD14n ＋＋单核细胞的相互作用及ALS可能的发病机制。n 方法:选择2013年1月至2019年12月于四川遂宁市中心医院就诊的ALS患者90例作为ALS组，同期随机选择健康志愿者30例作为对照组。用ALS患者和健康人血清外泌体刺激健康人和ALS患者CD14n ＋＋单核细胞，分析单核细胞因子的分泌功能。从HEK293细胞的条件培养基中制备Luc、TDP(WT)-Luc以及ALS突变型TDP(M337V)-Luc的外泌体，分别刺激ALS患者/健康人CD14n ＋＋单核细胞，分析单核细胞的吞噬功能和细胞因子的分泌功能。n 结果:健康人CD14n ＋＋单核细胞的分泌功能与外泌体供体相关性不大，不同组别外泌体培养下的健康人CD14n ＋＋单核细胞分泌的促炎细胞因子水平无明显差异(n P>0.05)；而不同组别外泌体培养下的ALS组CD14n ＋＋单核细胞分泌的促炎细胞因子表达水平存在显著差异，ALS患者单核细胞趋化蛋白-1(monocyte chemotactic protein 1，MCP-1)、白细胞介素(interleukin，IL)-6、IL-13的表达水平较对照组明显升高[(38.41±2.33)pg/mL比(35.15±2.42)pg/mL，(0.35±0.03)pg/mL比(0.29±0.02)pg/mL，(4.43±0.35)pg/mL比(4.15±0.23)pg/mL，n t值分别为2.143，1.537和1.574，n P值均0.05). The levels of proinflammatory cytokines secreted by CD14n + + monocytes were significantly different in ALS group cultured with different exosomes.The expression level of monocyte chemoattractant protein-1(MCP-1), interleukin(IL) -6 and IL-13 in ALS patients were significantly higher than those in controls [(38.41±2.33) pg/ mL vs(35.15±2.42) pg/mL, (0.35±0.03) pg/mL vs(0.29±0.02) pg/mL, (4.43±0.35) pg/mL vs(4.15±0.23) pg/mL, n t values were 2.143, 1.537 and 1.574 respectively, all n P values<0.05]. The relationship between the uptake of exosomes by CD14n + + monocytes and TDP-43 in exosomes were analyzed.The result showed that the uptake efficiency of CD14n + + monocytes to exosomes containing TDP-43 was 10 times higher than that of Luc exosomes, but the exosomes uptake of mutant TDP(m337v)-Luc in ALS patients was decreased, indicating that the phagocytic function of CD14n + + monocytes in ALS patients was impaired.In addition, compared with Luc exosomes, TDP(WT)-Luc exosomes increased the secretion functions of IL-6, IL-10, IL-1b and MCP-1 of CD14n + + monocytes in healthy subjects and ALS patients, while TDP(M337V)-Luc exosomes inhibited its secretion function.n Conclusions:Mutated TDP-43 in ALS may induce monocytes through loaded exosomes, resulting in the dysfunction of activation and phagocytosis of monocytes, leading to more TDP-43 accumulation in the central nervous system.