射血分数保留性心力衰竭患者外周血单个核细胞NLRP3表达水平及临床意义

Expression Level and Clinical Significance of NLRP3 in Peripheral Blood Mononuclear Cells of Patients with Heart Failure with Preserved Ejection Frac⁃tion

目的 研究外周血单个核细胞NOD样受体热蛋白结构域相关蛋白3(NOD-like receptor thermal protein domain associated protein 3,NLRP3)炎性小体在射血分数保留性心力衰竭(heart failure with preserved ejection fraction,HFpEF)患者中的表达及临床意义。方法 选取2018年1月至2021年1月在陆军军医大学大坪医院心血管内科就诊并确诊为HFpEF的患者120例为研究对象,同时选取同期50例无心力衰竭的患者为对照组。检测两组患者外周血单个核细胞NLRP3 mRNA、炎性细胞因子白细胞介素-1β(interleukin-1,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、心功能指标如左心室射血分数(left ventricular ejection fraction,LVEF)、左心室舒张末期内径(left ventricular end diastolic dimension,LVEDD)、左心室收缩末期内径(left ventricular end diastolic dimension,LVESD)及氨基末端脑钠肽前体(N-terminal pro-brain natriuretic peptide,NT-proBNP)浓度;记录H2FPEF评分。分别比较两组患者上述指标的差异,评价外周血单个核细胞NLRP3 mRNA对HFpEF患者早期诊断的评估价值。结果 与对照组比较,HFpEF组患者外周血单个核细胞NLRP3 mRNA和炎性指标(IL-1β、TNF-α)浓度显著升高,差异有统计学意义(P<0.05)。与对照组比较,HFpEF组患者的H2FPEF评分、NT-proBNP浓度显著升高,差异有统计学意义(P<0.05),而LVEF、LVEDD及LVESD比较,差异无统计学意义(P>0.05)。HFpEF组外周血单个核细胞NLRP3 mRNA浓度与IL-1β浓度、TNF-α浓度、H2FPEF评分及NT-proBNP浓度呈显著正相关(IL-1β:r=0.620,P=0.004;TNF-α:r=0.541,P=0.011;H2FPEF评分:r=0.653,P=0.002;NT-proBNP:r=0.596,P=0.007)。受试者工作特征曲线(receiver operating characteristic curve,ROC)分析表明,NLRP3 mRNA对HFpEF患者早期诊断的曲线下面积为0.779(95%CI:0.682~0.875),敏感度和特异度分别为75.00%和79.59%。结论 NLRP3炎性小体的激活可能与HFpEF的发生相关,通过检测外周血单个核细胞NLRP3 mRNA浓度,对HFpEF患者的早期诊断具有一定的临床价值。

Objectives To study the expression and clinical significance of NOD-like receptor thermal protein domain associated protein 3(NLRP3)inflammasome in peripheral blood mononuclear cells in patients with heart failure with preserved ejection fraction(HFpEF).Methods Totally 120 patients with HFpEF were selected as the research objects from January 2018 to January 2021 in Department of Cardiology,Daping Hospital,Army Medical University,and 50 patients without heart failure during the same period were selected as control group.The NLRP3 mRNA in peripheral blood mono-nuclear cells,inflammatory cytokines[interleukin-1(IL-1)β,tumor necrosis factor-α(TNF-α)],cardiac function indexes such as left ventricular ejection fraction(LVEF),left ventricular end-diastolic diameter(LVEDD),left ventricular end-systolic diameter(LVESD)and concentration of N-terminal pro-brain natriuretic peptide(NT-proBNP)were detected.The H2FPEF score was recorded.The differences of the above indicators between the two group were compared,and the early diagnosis value of NLRP3 mRNA in peripheral blood mononuclear cells in patients with HFpEF were evaluated.Results Compared with control group,the concentrations of NLRP3 mRNA in peripheral blood mononuclear cells and inflammatory indexes(IL-1β,TNF-α)in HFpEF group were significantly increased(P<0.05).Compared with control group,the H2FPEF score and concentration of NT-proBNP in HFpEF group were significantly increased(P<0.05),but there were no significant differences in LVEF,LVEDD and LVESD between control group and HFpEF group(P>0.05).The concentration of NLRP3 mRNA in peripheral blood mononuclear cells in HFpEF group was significantly positively correlated with H2FPEF scores,concentrations of IL-1β,TNF-αand NT-proBNP(IL-1β:r=0.620,P=0.004;TNF-α:r=0.541,P=0.011;H2FPEF score:r=0.653,P=0.002;NT-proBNP:r=0.596,P=0.007).Receiver operating characteristic curve(ROC)analysis showed that the area under the curve of NLRP3 mRNA for early diagnosis of HFpEF patients and specificity were 0.779(95%CI:0.682-0.875),and the sensitivity and specificity were 75.00%and 79.59%,respectively.Conclusions The activation of NLRP3 inflammasome may be related to the occurrence of HFpEF.By detecting the concentration of NLRP3 mRNA in peripheral blood mononuclear cells,it has certain clinical value for the early diagnosis of HFpEF patients.