NLRC4介导的炎症小体通路与多发性骨髓瘤的关系及治疗前景  

The relationship between NLRC4-mediated inflammasome pathway and multiple myeloma and its therapeutic prospect

作　　者：许婷婷 汪万杰 鲍静[1] 夏瑞祥[1] XU Tingting;WANG Wanjie;BAO Jing;XIA Ruixiang(Department of Hematology,The First Affiliated Hospital of Anhui Medical University,Hefei 230032,Anhui,China)

机构地区：[1]安徽医科大学第一附属医院血液科,安徽合肥230032

出　　处：《中国临床药理学与治疗学》2025年第4期501-508,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省自然科学基金(2008085MH296);安徽医科大学自然科学基金项目(2020xkjl86);安徽省教育厅自然科学研究项目(2022AH051178)。

摘　　要：目的:通过分析NLRC4 mRNA在多发性骨髓瘤(multiple myeloma,MM)患者骨髓液中的相对表达及临床意义,探究NLRC4在多发性骨髓瘤中的作用机制及临床意义,以此指导疾病治疗方案的制定及临床预后的评估。方法:通过MMRF数据库及GTEx数据库比较炎症小体在骨髓瘤患者与正常对照中的表达差异及生存相关性。通过实时荧光定量聚合酶链式反应(qPCR)法检测2023年1月至2023年9月于安徽医科大学第一附属医院收治的26例初诊骨髓瘤患者及19例治疗后骨髓瘤患者的骨髓液与28例正常志愿者外周血中炎症小体的表达,分析各炎症小体mRNA的表达差异及NLRC4炎症小体的表达与初诊患者临床病理特征、炎症因子/趋化因子表达的相关性。结果:与对照组和治疗后组相比,除NLRP3外,初诊组中炎症小体mRNA的表达均升高,其中NLRC4 mRNA表达明显升高(P<0.01)。初诊患者中血红蛋白计数、肌酐水平及钙离子水平与NLRC4 mRNA表达水平呈直线相关(P<0.05)。初诊患者中IL-18、CCL-3与NLRC4 mRNA表达水平呈直线相关(P<0.05)。结论:在多发性骨髓瘤中,NLRC4炎症小体呈高表达,并通过促进炎症因子/趋化因子IL-18、CCL-3的生成及释放促进肿瘤的发生发展,对多发性骨髓瘤治疗方案的制定及临床预后的评估具有重要意义。AIM:To explore the mechanism of action and clinical significance of NLRC4 in multiple myeloma by analyzing the relative expression and clinical significance of NLRC4 mRNA in bone marrow fluid of patients with multiple myeloma(MM),so as to guide the formulation of disease treatment and the evaluation of clinical prognosis.METHODS:MMRF database and GTEx database were used to compare the expression and survival correlation of inflammatory bodies between myeloma patients and normal controls.Real-time fluorescent quantitative polymerase chain reaction(qPCR)was used to detect the expression of inflammatory bodies in bone marrow fluid of 26 newly diagnosed myeloma patients and 19 post-treatment myeloma patients and peripheral blood of 28 normal volunteers admitted to the First Affiliated Hospital of Anhui Medical University from January to September 2023.The mRNA expression differences of each inflammatory body and the correlation between NLRC4 inflammatory body expression and clinicopathologic features,inflammatory factor/chemokine expression of newly diagnosed patients were analyzed.RESULTS:Compared with the control group and the treatment group,the expression of inflammasome mRNA in the newly diagnosed group was increased except for NLRP3,and the expression of NLRC4 mRNA was significantly increased(P<0.01).The hemoglobin count,creatinine level and calcium ion level were linearly correlated with NLRC4 mRNA expression level in newly diagnosed patients(P<0.05).The mRNA expression levels of IL-18,CCL-3 and NLRC4 in newly diagnosed patients were linearly correlated(P<0.05).CONCLUSION:NLRC4 inflammatosomes are highly expressed in MM,and promote the occurrence and development of tumor by promoting the production and release of inflammatory cytokines/chemokines IL-18 and CCL-3,which is of great significance for the formulation of treatment plan and clinical prognosis evaluation of multiple myeloma.

关 键 词：多发性骨髓瘤 炎症小体 NLRC4 治疗方案 临床预后 

分 类 号：R969[医药卫生—药理学] R559[医药卫生—药学]