【摘要】 目的：探究结直肠癌来源的外泌体对巨噬细胞极化的影响及其作用机制。方法：建立THP-1来源的M2型巨噬细胞体外诱导分化模型，利用流式细胞染色实验检测细胞分化效率；通过与结直肠癌细胞共培养、结直肠癌细胞外泌体干预M2型巨噬细胞分化，利用实时荧光定量PCR实验检测ARG1、IL-10和NLRP3 mRNA的表达水平。结果：体外诱导分化的M2型THP-1巨噬细胞CD163阳性细胞比例显著升高；与对照组相比，与结直肠癌细胞HCT8和HCT116共培养的M2型巨噬细胞ARG1、IL-10表达水平显著升高，NLRP3表达水平下降。与转染阴性对照microRNA（miR-NC）组相比，转染miR-34a inhibitor的HCT8和HCT116共培养或外泌体刺激下，M2型巨噬细胞ARG1、IL-10表达水平下降，NLRP3表达水平升高；与miR-NC组相比，转染miR-34a inhibitor的THP-1细胞ARG1、IL-10表达水平显著下降，NLRP3表达水平显著升高。结论：结直肠癌细胞来源的外泌体miR-34a可以抑制巨噬细胞NLRP3的表达，促进巨噬细胞M2型极化。更多还原

【Abstract】 Objective: To investigate the effect of colorectal cancer derived exosomes on macrophage polarization and the underlying mechanism. Methods: The THP-1-derived M2 macrophage differentiation model was established in vitro, and the cell differentiation efficiency was detected by flow cytometry assay. Colorectal cancer cells were co-cultured and colorectal cancer exosomes were isolated to intervene the differentiation of M2-type macrophages. The mRNA expression levels of ARG1, IL-10 and NLRP3 were detected by real-time qPCR. Results: The population of CD163+ differentiated THP-1 cells was significantly increased. Compared with control group, the expression levels of ARG1 and IL-10 in M2 macrophages co-cultured with colorectal cancer cells HCT8 and HCT116 were significantly increased, while the expression level of NLRP3 was decreased. Compared with miR-NC group, the expression levels of ARG1 and IL-10 in M2 macrophages under the co-culture of HCT8 and HCT116 transfected with miR-34a inhibitor or the stimulation of exosomes were decreased, while the expression level of NLRP3 was increased. Compared with miR-NC group, the expression levels of ARG1 and IL-10 in THP-1 cells transfected with miR-34a inhibitor were significantly decreased, while the expression level of NLRP3 was significantly increased. Conclusion: The colorectal cancer cells derived-exosomal miR-34a could inhibit the expression of NLRP3 in macrophages and promote M2 macrophages polarization.更多还原