非酒精性脂肪性肝病患者血清HIF-1α、HMGB1和脂联素水平变化及其与颈动脉粥样硬化的关系研究

Changes of serum HIF-1α,HMGB1 and adiponectin levels in patients with non-alcoholic fatty liver diseases and their correlation to carotid atherosclerosis

目的探讨非酒精性脂肪性肝病(NAFLD)患者血清低氧诱导因子-1α(HIF-1α)、高迁移率族蛋白1(HMGB1)和脂联素(APN)水平变化及其与颈动脉粥样硬化(CAS)的关系。方法2018年5月~2023年3月我院诊治的NAFLD患者158例(其中合并CAS者71例),使用Fibrotouch弹性成像仪诊断脂肪肝,使用超声诊断仪检测颈动脉斑块形成。采用ELISA法检测血清HIF-1α、HMGB1和APN水平,应用二元Logistic回归分析NAFLD合并CAS的影响因素,应用受试者工作特征曲线下面积(AUC)评估血清指标预测NAFLD患者合并CAS的效能。结果合并CAS组收缩压为(137.1±10.3)mmHg,显著高于未合并CAS组【(132.9±8.2)mmHg,P<0.05】;合并CAS组血清TC、LDL-C、HIF-1α和HMGB1水平分别为(6.5±2.3)mmol/L、(3.7±0.6)mmol/L、(25.7±6.5)pg/L和(9.4±2.3)ng/ml,显著高于未合并CAS组【分别(5.1±1.7)mmol/L、(2.8±0.3)mmol/L、(17.2±4.1)pg/L和(6.1±1.5)ng/ml,P<0.05】,而血清APN为(7.5±3.0)mg/L,显著低于未合并CAS组【(12.8±4.6)mg/L,P<0.05】;多因素Logistic回归分析显示,TC(OR=1.411,95%CI:1.133~1.757)、LDL-C(OR=1.419,95%CI:1.128~1.785)、HIF-1α(OR=1.504,95%CI:1.182~1.914)、HMGB1(OR=1.520,95%CI:1.206~1.916)和APN(OR=1.530,95%CI:1.226~1.909)均是影响NAFLD患者合并CAS的独立危险因素(P<0.05);ROC曲线分析显示,血清HIF-1α、HMGB1和APN水平联合预测NAFLD患者合并CAS的AUC为0.863,其敏感度为94.5%,特异度为75.0%,优于各指标单独预测(P<0.05)。结论NAFLD患者血清HIF-1α和HMGB1水平升高而血清APN水平降低是发生CAS的危险因素,应及时发现和给予必要的干预。

Objective The aim of this study was to investigate the changes of serum hypoxia inducible factor-1α(HIF-1α),high-mobility group box 1(HMGB1)and adiponectin(APN)levels in patients with non-alcoholic fatty liver diseases(NAFLD)and their correlation to carotid atherosclerosis(CAS).Methods 158 patients with NAFLD,including concomitant CAS in 71 cases,were encountered in our hospital between May 2018 and March 2023,and the NAFLD was diagnosed based on Fibrotouch detection and the CAS was determined by ultrasonography.Serum HIF-1α,HMGB1 and APN levels were assayed by ELISA,the risk factors was revealed by multivariate Logistic regression analysis and predicting performance was evaluated by the area under the receiver operating characteristic curve(AUC).Results The systolic blood pressure in patients NAFLD and concomitant CAS was(137.1±10.3)mmHg,much higher than[(132.9±8.2)mmHg,P<0.05]in NAFLD patients without CAS;serum TC,LDL-C,HIF-1αand HMGB1 levels were(6.5±2.3)mmol/L,(3.7±0.6)mmol/L,(25.7±6.5)pg/L and(9.4±2.3)ng/ml,all significantly higher than[(5.1±1.7)mmol/L,(2.8±0.3)mmol/L,(17.2±4.1)pg/L and(6.1±1.5)ng/ml,respectively,P<0.05],while serum APN level was(7.5±3.0)mg/L,much lower than[(12.8±4.6)mg/L,P<0.05]in those without CAS;the multivariate Logistic regression analysis showed that serum TC(OR=1.411,95%CI:1.133-1.757),LDL-C(OR=1.419,95%CI:1.128-1.785),HIF-1α(OR=1.504,95%CI:1.182-1.914),HMGB1(OR=1.520,95%CI:1.206-1.916)and APN(OR=1.530,95%CI:1.226-1.909)were all the risk factors impacting CAS occurrence in patient with NAFLD(P<0.05);the ROC analysis demonstrated that the AUC was 0.863,with the sensitivity of 94.5%and the specificity of 75.0%when the combination of serum HIF-1α,HMGB1 and APN levels was applied to predict the CAS existence,much superior to any single parameter did(P<0.05).Conclusion The elevated serum HIF-1αand HMGB1 levels and the decreased serum APN level are all risk factors for the occurrence of CAS in patients with NAFLD,which might be intervened as sooner as possible.