Expression and correlation of HMGB1 and LncRNA Peg13 levels in peripheral blood of sepsis patients
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目的:探讨脓毒症患者外周血中高迁移率族蛋白B1(HMGB1)及长链非编码RNA(LncRNA)Peg13的表达及其临床价值.方法:选取2021年6月至2022年12月浙江省绍兴市人民医院收治的脓毒症患者44例,另纳入同期健康体检患者(非脓毒症)36例作为对照组,采用酶联免疫吸附法(ELISA)检测外周血中HMGB1的含量,采用实时荧光定量PCR(RT-PCR)法检测外周血LncRNA Peg13相对表达量,采用Spearman及Pearson相关性检验评价外周血HMGB1、LncRNA Peg13以及炎症因子对脓毒症的诊断价值,并分析LncRNA Peg13的表达与HMGB1及炎症指标(WBC、CRP、PCT、ESR)和细胞因子(IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ)的相关性.同时将脓毒症组分别按照是否发生多器官功能障碍及是否发生休克进行危险分层,分析外周血HMGB1、LncRNA Peg13与疾病严重程度的相关性.结果:脓毒症组外周血HMGB1含量(pg/mL)高于非脓毒症组(2 965.18±1 389.71 vs 27.64±8.56,P<0.001);且LncRNA Peg13在脓毒症组中的相对表达量高于非脓毒症组(20.80±8.07 vs 0.00±0.00,P<0.001).外周血HMGB1用于脓毒症诊断的ROC曲线下面积(AUC)、灵敏度、特异度分别为0.909(95%CI:0.824～0.962,P<0.000 1),90.91%,100%;外周血LncRNA Peg13用于脓毒症诊断的AUC、灵敏度、特异度分别为 0.989(95%CI:0.934～1.000,P<0.000 1),97.93%,100%.脓毒症组患者外周血HMGB1 水平与外周血LncRNA Peg13相对表达量呈一定负相关(r=-0.521,P<0.001),与外周血CRP水平及ESR水平呈正相关(r=0.516,r=0.310,P<0.001);与外周血WBC、PCT、IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ水平无明显相关性.脓毒症组患者外周血LncRNA Peg13相对表达量与外周血CRP水平及ESR水平呈负相关(r=-0.375,r=-0.315,P<0.05);与外周血WBC、PCT、IL-2、IL-4、IL-6、IL-10、TNF-α、IFN-γ水平无明显相关性.脓毒症组中MODS组外周血 HMGB1 含量(pg/mL)高于非 MODS 组(3 748.90±637.72 vs 2 249.84±1 082.71,P<0.001),而LncRNA Peg13相对表达量MODS组低于非MODS组(18.95±5.96 vs 25.64±8.27,P=0.004);脓毒症组中休克组与非休克组之间外周血HMGB1含量与LncRNA Peg13相对表达量无明显差异.结论:脓毒症患者中HMGB1含量及LncRNA Peg13表达水平显著上调,两者含量呈负相关.且HMGB1水平对疾病的严重程度有一定的预测价值.
Objective:To investigate the expression and clinical significance of high mobility group box 1 protein(HMGB1)and long noncoding RNA(LncRNA)Peg13 in patients with sepsis.Methods:A to-tal of 44 patients with sepsis in Shaoxing People's Hospital from June 2021 to December 2022 were se-lected as the sepsis group,and 36 healthy subjects in the same period were selected as the control group.The plasma level of HMGB1 was detected by enzyme-linked immunosorbent assay(ELISA).The relative expression of LncRNA Peg13 was detected by quantitative real-time polymerase chain re-action(RT-PCR).The correlation between the expression of HMGB1,LncRNA Peg13,and inflam-matory cytokines including WBC,CRP,PCT,ESR and IL-2,IL-4,IL-6,IL-10,TNF-α,and IFN-γ was analyzed using Spearman and Pearson method.The correlation between the expression of HMGB1,lncRNA Peg13,and the severity of sepsis was analyzed.Results:Compared with the con-trol group,serum HMGB1 of patients in sepsis increased as(2 965.18±1 389.71)vs(27.64±8.56)pg/mL,P<0.001,and the relative expression of LncRNA Peg13 increased as 20.80±8.07 vs 0.00±0.00,P<0.001.The area under the receiver operator characteristic(ROC)curve of HMGB1 and the relative expression of LncRNA Peg13 for the diagnosis of sepsis were 0.909(95%CI:0.824-0.962,P<0.000 1)and 0.989(95%CI:0.934-1.000,P<0.000 1).In the sepsis group,HMGB1 was negatively correlated with the relative expression of LncRNA Peg13(r=-0.521,P<0.001),and it was positively correlated with CRP and ESR(r=0.516,r=0.310,both P<0.001),which did not correlate with either of WBC,PCT,IL-2,IL-4,IL-6,IL-10,TNF-α,and IFN-γ.The relative expression of LncRNA Peg13 was negatively correlated with CRP and ESR(r=-0.375,r=-0.315,P<0.05),which did not correlate with either of WBC,PCT,IL-2,IL-4,IL-6,IL-10,TNF-α,and IFN-γ.HMGB1 increased in MODS patients,as(3 748.90±637.72)pg/mL vs(2 249.84±1 082.71)pg/mL,P<0.05,and relative expression of LncRNA Peg13 decreased in MODS patients,as 18.95±5.96 vs 25.64±8.27,P=0.004.No significant dif-ference in HMGB1 and relative expression of LncRNA Peg13 was found between shock and non-shock subgroups in sepsis patients.Conclusion:HMGB1 and the relative expression of LncRNA Peg13 increase in sepsis patients,which can help the early diagnosis of sepsis,and HMGB1 could be used as an indicator to predict the severity of sepsis.
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