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异柠檬酸脱氢酶1及其产物在肝衰竭患者的表达与临床意义
作者:邓威  陈倩  石春霞  郭金  张璐懿  龚作炯 
单位:武汉大学人民医院 感染科 湖北 武汉 430060 
关键词:肝衰竭 异柠檬酸脱氢酶1 烟酰胺腺嘌呤二核苷酸磷酸 
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出版年,卷(期):页码:2023,15(3):50-55
摘要:
摘要:目的 探讨肝衰竭患者血清异柠檬酸脱氢酶1(isocitrate dehydrogenase 1,IDH1) 及其产物的水平变化,分析其作用及潜在作用机制。方法 回顾性分析2019年2月至2019 年12月在武汉大学人民医院就诊的肝硬化患者(40例)、肝衰竭患者(30例)、肝 衰竭合并感染者(30例)及健康体检者(20例)的临床资料。采集各组血清,检 测各组IDH1水平、活化部分凝血活酶时间(activated partial thromboplastin time, APTT)、凝血酶原时间(prothrombin time,PT)、凝血酶原活动度(prothrombin time activity,PTA)、丙氨酸氨基转移酶(alanine transaminase,ALT)、天门冬氨 酸氨基转移酶(aspartate amino transferase,AST)、白蛋白(albumin,ALB)、总 胆红素(total bilirubin,TBil)、白细胞计数(white blood cell count,WBC)、中性 粒细胞比例(neutrophil ratio,Neu%)、血小板计数(platelet count,PLT)、红细胞 计数(red blood cell count,RBC)、血红蛋白(hemoglobin,Hb)及超敏C-反应蛋白 (hs C-reactive protein,hs-CRP)水平,检测血清异柠檬酸、α-酮戊二酸及NADPH丰 度。采用Spearman相关分析探究临床生物化学指标与IDH1的相关性,采用二元Logistic 回归分析肝衰竭患者发生感染的影响因素,采用受试者工作特征(receiver operating characteristic,ROC)曲线评估影响因素对肝衰竭患者发生感染的价值。结果 对照 组、肝硬化组、肝衰竭组及肝衰竭合并感染组血清IDH1水平依次升高(中位数: 15.35 U/L vs 34.69 U/L vs 75.26 U/L vs 135.82 U/L),差异有统计学意义(H = 105.70, P < 0.001)。血清IDH1水平与ALT、AST及TBil呈正相关(r值分别为0.884、0.876、 0.830,P均< 0.001),与PTA呈负相关(r = -0.626,P < 0.001)。肝衰竭组IDH1底物 异柠檬酸丰度较对照组增加(929982.67 ± 187082.79 vs 261854.12 ± 116906.79),产物 α-酮戊二酸丰度较对照组降低(1375241.56 ± 235207.2 vs 4362813.42 ± 635864.95),肝 衰竭组NADPH丰度较对照组降低(495.99 ± 48.83 vs 916.13 ± 101.16),差异均有统计 学意义(t = -3.029,P = 0.009;t = 4.407,P = 0.001;t = 3.740,P = 0.002)。Logistic 多因素回归分析表明,IDH1和hs-CRP为肝衰竭患者发生感染的独立危险因素(OR = 1.088,95%CI:1.042~1.136,P < 0.001;OR = 1.059,95%CI:1.042~1.136,P = 0.049)。IDH1预测肝衰竭患者发生感染的ROC曲线下面积为0.847,显著高于hs-CRP (0.651;z = 2.107,P = 0.035)。结论 IDH1在肝衰竭诊断中具有一定价值,与肝衰竭 发展具有一定关系,是评估肝衰竭患者发生感染的独立危险因素。
Abstract: Objective To investigate the level of isocitrate dehydrogenase 1 (IDH1) and its products in patients with liver failure and to analyze its effects and potential mechanisms. Methods The clinical data of patients with liver cirrhosis (40 cases), patients with liver failure (30 cases), liver failure patients complicated with infection (30 cases) and healthy subjects (20 cases) in Renmin Hospital of Wuhan University from February 2019 to December 2019 were analyzed retrospectively. The serum of each group was collected and the levels of IDH1, activated partial thromboplastin time (APTT), prothrombin time (PT), prothrombin time activity (PTA), alanine transaminase (ALT), aspartate amino transferase (AST), albumin (ALB), total bilirubin (TBil), white blood cell count (WBC), neutrophil ratio (Neu%), platelet count (PLT), red blood cell count (RBC), hemoglobin (Hb) and hs C-reactive protein (hs-CRP) were detected. The abundance of serum isocitrate, α-ketoglutarate and NADPH were also measured. Spearman correlation analysis was used to explore the correlation between clinical biochemical indexes and IDH1. Binary Logistic regression was used to analyze the influencing factors of infection in patients with liver failure. The receiver operating characteristic (ROC) curve was used to evaluate the value of influencing factors for infection in patients with liver failure. Results The serum IDH1 levels of patients in control group, liver cirrhosis group, liver failure group and liver failure combined with infection group increased sequentially (median: 15.35 U/L vs 34.69 U/L vs 75.26 U/L vs 135.82 U/L), the difference was statistically significant (H = 105.70, P < 0.001). The level of serum IDH1 was positively correlated with ALT, AST and TBil, respectively (r = 0.884, 0.876, 0.830, all P < 0.001), and negatively correlated with PTA (r = -0.626, P < 0.001). Compared with those of control group, the abundance of IDH1 substrate isocitratein in liver failure group increased (929982.67 ± 187082.79 vs 261854.12 ± 116906.79), α-ketoglutarate (1375241.56 ± 235207.2 vs 4362813.42 ± 635864.95) and NADPH (495.99 ± 48.83 vs 916.13 ± 101.16) decreased, the differences were statistically significant (t = -3.029, P = 0.009; t = 4.407, P = 0.001; t = 3.740, P = 0.002). Multivariate Logistic regression analysis showed that IDH1 and hs-CRP are independent risk factors for infection in patients with liver failure (OR = 1.088, 95%CI: 1.042~1.136, P < 0.001; OR = 1.059, 95%CI: 1.042~1.136, P = 0.049). The area under the ROC curve for IDH1 predicted infection in patients with liver failure was 0.847, which was significantly higher than that of hs?CRP (0.651; z = 2.107, P = 0.035). Conclusion IDH1 had a certain value in the diagnosis of liver failure, had a certain relationship with the development of liver failure, and could be used as an independent factor to evaluate the occurrence of infection in patients with liver failure.
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