乙型肝炎肝硬化并发自发性细菌性腹膜炎患者外周血单个核细胞NLRP3和Caspase-1水平变化及其临床意义探讨

Predictive performance of peripheral blood mononuclear cell NLRP3 and caspase-1 mRNA levels in patients with hepatitis B cirrhosis and complicated spontaneous bacterial peritonitis

目的 探讨乙型肝炎肝硬化并发自发性细菌性腹膜炎(SBP)患者外周血单个核细胞(PBMCs)核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)和半胱氨酸蛋白酶1(caspase-1)水平变化及其预测预后的价值。方法 2018年1月~2020年5月我院诊治的乙型肝炎肝硬化并发SBP患者65例,采用PCR法检测PBMCs NLRP3和Caspase-1 mRNA水平,采用ELISA法检测血清血白介素-1β(IL-1β)和IL-18水平。应用受试者工作特征曲线并计算曲线下面积(AUC)分析各指标对患者预后的预测价值。结果 21例重症组PBMCs NLRP3和Caspase-1 mRNA水平及血清IL-1β和IL-18水平分别为(1.5±0.3)和(2.0±0.4)、(11.7±2.1)pg/mL和(17.4±1.6)pg/mL,显著高于44例轻症组【分别为(1.1±0.2)和(1.6±0.3)、(8.6±1.3)pg/mL和(12.1±1.3)pg/mL,P<0.05】;应用PBMCs NLRP3联合Caspase-1水平评估SBP患者病情严重程度的AUC为0.899,SE(95%CI)=0.036(0.828~0.971);15例死亡组PBMCs NLRP3和Caspase-1 mRNA水平及血清IL-1β和IL-18水平分别为(1.7±0.3)和(2.3±0.5)、(12.5±2.2)pg/mL和(18.2±3.1)pg/mL,显著高于50例生存组【分别为(1.1±0.2)和(1.6±0.3)、(8.9±1.8)pg/mL和(12.7±2.5)pg/mL,P<0.05】;应用PBMCs NLRP3联合Caspase-1水平预测患者预后的AUC为0.916,SE(95%CI)=0.043(0.831~0.999)。结论 乙型肝炎肝硬化并发SBP患者PBMCs NLRP3和Caspase-1水平升高,可能与病情严重程度相关,其机制仍需要研究。

Objective The aim of this study was to explore the predictive efficacy of peripheral blood mononuclear cells(PBMCs)nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)and cysteine protease-1(caspase-1)mRNA levels in patients with hepatitis B cirrhosis and complicated spontaneous bacterial peritonitis(SBP).Methods 65 patients with hepatitis B cirrhosis complicated by SBP were enrolled in our hospital between January 2018 and May 2020.The PBMC NLRP3 and caspase-1 mRNA levels were detected by real-time fluorescence quantitative PCR and serum interleukin-1β(IL-1β)and IL-18 levels were detected by ELISA.The predictive performance was evaluated by the area under receiver operating characteristic curve(AUC).Results The PBMCs NLRP3,caspase-1 mRNA and serum IL-1βand IL-18 levels in 21 patients with severe SBP were(1.5±0.3),(2.0±0.4),(11.7±2.1)pg/mL and(17.4±1.6)pg/mL,all significantly higher than[(1.1±0.2),(1.6±0.3),(8.6±1.3)pg/mL and(12.1±1.3)pg/mL,respectively,P<0.05]in 44 patients with mild SBP;the AUC was 0.899,with SE(95%CI)of 0.036(0.828-0.971),when predicting severe disease by the combination of PBMCs NLRP3 and caspase-1 levels;the PBMCs NLRP3,caspase-1 mRNA and serum IL-1βand IL-18 levels in 15 dead patients at presentation were(1.7±0.3),(2.3±0.5),(12.5±2.2)pg/mL and(18.2±3.1)pg/mL,all significantly higher than[(1.1±0.2),(1.6±0.3),(8.9±1.8)pg/mL and(12.7±2.5)pg/mL,respectively,P<0.05]in 50 survivals;the AUC was 0.916,with SE(95%CI)of 0.043(0.831-0.999),when predicting the prognosis of patients with SBP by the combination of PBMCs NLRP3 and caspase-1 mRNA levels.Conclusion The PBMCs NLRP3 and caspase-1 levels increase in patients with hepatitis B cirrhosis complicated by SBP,which might be related to the severity of the entity and needs further investigation.