【摘要】 目的 检测多发性骨髓瘤(multiple myeloma, MM)患者骨髓中缺氧诱导因子-1α(hypoxia-inducible factor, HIF-1α)表达、T淋巴细胞分化、T淋巴细胞中耗竭相关基因表达，并探究HIF-1α与T淋巴细胞分化的相关性。方法 收集2021年1月～2022年2月华中科技大学同济医学院附属武汉市中心医院收治的9例MM患者(MM组)和3例缺铁性贫血(iron deficiency anemia, IDA)患者(IDA组)的病例资料，采用免疫组化方法检测两组患者骨髓中HIF-1α的表达阳性率，采用流式细胞学分析两组患者辅助性T细胞17(T helper cell 17, Th17)、调节性T淋巴细胞(regulatory T cell, Treg)、Th22占CD4~+T淋巴细胞中的百分比，采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction, RT-qPCR)检测两组患者T淋巴细胞中耗竭相关基因的表达。采用Pearson相关性评价HIF-1α与T淋巴细胞分化指标的相关性。结果 MM组患者骨髓标本中HIF-1α表达阳性率，外周血中Th17/Treg和Th22占CD4~+T淋巴细胞中的百分比，T淋巴细胞耗竭相关基因NFATc1表达水平均高于IDA组。HIF-1α表达水平与Th22呈正相关，Th17/Treg与溶骨性病变程度呈正相关。结论 MM患者中，Th17/Treg、Th22水平和T淋巴细胞耗竭相关基因上调，存在T淋巴细胞分化和功能异常，且骨髓中高表达的HIF-1α与Th17/Treg和Th22水平呈正相关。更多还原

【Abstract】 Objective To investigate the expression of hypoxia-inducible factor(HIF-1α) in bone marrow samples of multiple myeloma(MM) patients, T-cell differentiation and the gene expression exhaust-related genes in T-cell, analyze the correlation between HIF-1α and T-cell differentiation. Methods The clinical data of 9 MM patients(MM group) and 3 IDA patients(IDA group) admitted to The Central Hospital of Wuhan, Tongji Medical College of Huazhong University of Science and Technolog from January 2021 to February 2022 were collected. The positive rate of HIF-1α in bone marrow of the two groups was detected by immunohistochemistry technique, the percentage in CD4~+T-cell of T helper cell lymphocyte 17(Th17), regulatory T lymphocyte(Treg) and Th22 in the two groups were analyzed by flow cytometry, the expression of exhaust-related genes in T-cell of the two groups was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR). The correlation between HIF-1α and T-cell differentiation was evaluated by Pearson correlation. Results The positive rate of HIF-1α expression in bone marrow samples, the percentage in CD4~+T-cell of Th17/Treg, Th22 in peripheral blood, and the expression levels of exhaust-related gene NFATc1 in MM group were higher than those in IDA group(P<0.05). The expression level of HIF-1α was positively correlated with Th22, and Th17/Treg was positively correlated with the degree of osteolytic lesions. Conclusion In patients with MM, the levels of Th17/Treg, Th22 and T-cell exhaust-related genes are up-regulated, and abnormal T-cell differentiation and function are observed, and high expression of HIF-1α in bone marrow was associated with elevated Th17/Treg and Th22.更多还原