急性药物性肝损伤患者血清中核因子E2相关因子2和血红素加氧酶-1的含量及临床意义  

Serum levels and clinical significance of Nrf2 and HO-1 in patients with acute drug-induced liver injury

作　　者：张晓倩 杨慧[1] 孟蝶 张晓华 ZHANG Xiaoqian;YANG Hui;MEND Die;ZHANG Xiaohua(Department of Infectious Diseases,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一医院感染科,山西太原030001

出　　处：《胃肠病学和肝病学杂志》2020年第5期571-575,共5页Chinese Journal of Gastroenterology and Hepatology

基　　金：山西省卫生计生委科研课题(201601030);山西省重点研发计划(指南)项目(201803D42064)。

摘　　要：目的观察核因子E2相关因子2(Nrf2)和血红素加氧酶-1(HO-1)在急性药物性肝损伤(acute drug-induced liver injury, ADILI)患者血清中的含量及临床意义。方法收集ADILI患者60例,及60名健康对照者的外周血并分离血清,采用ELISA法检测样本中Nrf2及HO-1的含量,比较两组中Nrf2及HO-1的差异,并分析二者与疾病临床特征及生化指标的相关性。结果 Nrf2、HO-1在ADILI患者血清中的含量显著高于健康对照组,差异均有统计学意义(P<0.05);胆汁淤积型ADILI患者血清中Nrf2的含量显著高于肝细胞损伤型(P<0.001),HO-1的含量在胆汁淤积型、肝细胞损伤型及混合型中差异无统计学意义(P>0.05);Nrf2、HO-1与肝损伤指标丙氨酸氨基转移酶(ALT)、天门冬氨酸转氨酶(AST)、总胆红素(TBIL)、直接胆红素(DBIL)及胆汁酸(TBA)呈负相关(P<0.05);而与碱性磷酸酶(ALP)、谷氨酰基转移酶(GGT)无明显相关性(P>0.05);以Nrf2=516.14 U/L作为最佳截断值,预测ADILI疾病的敏感度为95.0%,特异度为77.1%,曲线下面积为0.918(P<0.05);以HO-1=15.19 U/L作为最佳截断值,预测的该疾病的敏感度为75.1%,特异度为60.9%,曲线下面积为0.799(P<0.05)。结论 Nrf2、HO-1在ADILI患者血清中的含量明显升高,且与肝细胞损伤程度呈负相关,二者在血清中的水平可以作为ADILI疾病程度较为敏感的预测指标。Objective To observe the serum levels and clinical significance of Nrf2 and HO-1 in patients with acute drug-induced liver injury(ADILI). Methods The peripheral blood of 40 patients with ADILI and 40 healthy controls were collected and serum was separated. The levels of Nrf2 and HO-1 in the samples were detected by ELISA. The differences of Nrf2 and HO-1 in the two groups were compared. The correlation of levels of Nrf2 and HO-1 with the clinical characteristics and biochemical indicators of the disease were analyzed. Results The serum levels of Nrf2 and HO-1 in serum of patients with ADILI were significantly higher than those in healthy control group, the difference was statistically significant(P<0.05);the serum level of Nrf2 in patients with cholestasis-induced ADILI was significantly higher than that in hepatocyte injury type(P<0.001). There was no significant difference among cholestasis type, hepatocyte injury type and mixed type(P>0.05). Nrf2 and HO-1 were negatively correlated with liver injury indexes ALT, AST, TBIL, DBIL and TBA(P<0.05);Nrf2 and HO-1 were not related with ALP and GGT(P>0.05);when Nrf2 = 516.14 U/L as the best cutoff value, the sensitivity of predicting ADILI disease was 95.0%, the specificity was 77.1%, and the area under the curve was 0.918(P<0.05);HO-1=15.19 U/L as the best cut-off value, the predicted sensitivity of the disease was 75.1%, the specificity was 60.9%, and the area under the curve was 0.799(P<0.05). Conclusion The serum levels of Nrf2 and HO-1 in patients with ADILI are significantly increased, and negatively correlated with the degree of hepatocyte injury. The serum levels of Nrf2 and HO-1 can be used as predictors of the degree of ADILI.

关 键 词：核因子E2相关因子2 血红素加氧酶-1 药物性肝损伤 氧化应激 

分 类 号：R575[医药卫生—消化系统]