孕期药物性肝损伤患者血清miR-21、Nrf2和HO-1水平变化及其临床意义探讨

Serum miR-21, Nrf2 and HO-1 level changes in pregnant women with drug-induced liver injury

目的 探讨孕期药物性肝损伤(DILI)患者血清微小RNA-21(miR-21)、核因子相关因子2(Nrf2)和血红素氧合酶-1(HO-1)水平变化及其临床意义。方法 2017年8月~2021年9月我院收治的83例DILI孕妇和58例同期产检的健康孕妇,采用实时荧光定量PCR法检测血清miR-21水平,采用ELISA法检测血清Nrf2和HO-1水平。结果 在本组83例DILI患者中,肝细胞损伤型53例、胆汁淤积型21例和混合型9例;肝损伤1级31例、2级32例、3级16例和4级4例;妊娠结局良好67例,结局不良(早产、死胎和胎儿宫内生长迟缓)16例;DILI组血清miR-21、Nrf2和HO-1水平分别为(1.5±0.2)、(537.4±53.8)U/L和(16.7±3.1)U/L,显著高于健康孕妇组【分别为(0.4±0.1)、(203.5±47.2)U/L和(11.4±2.2)U/L,P<0.05】;胆汁淤积型患者血清miR-21和Nrf2水平分别为(2.1±0.4)和(574.6±37.2)U/L,显著高于肝细胞损伤型【分别为(1.3±0.2)和(521.8±39.5)U/L,P<0.05】或混合型患者【分别(1.5±0.2)和(542.1±34.8)U/L,P<0.05】,混合型患者血清miR-21水平显著高于肝细胞损伤型患者(P<0.05);4级肝损伤患者血清miR-21、Nrf2和HO-1水平分别为(2.3±0.4)、(589.0±35.1)U/L和(21.5±2.8)U/L,显著高于3级患者【分别为(1.7±0.3)、(573.2±38.6)U/L和(19.1±1.8)U/L,P<0.05】,或2级患者【分别为(1.5±0.3)、(539.5±45.3)U/L和(16.4±2.5)U/L,P<0.05】,或1级患者【分别为(1.2±0.2)、(503.7±41.0)U/L和(14.5±2.1)U/L,P<0.05】;妊娠结局不良组血清miR-21、Nrf2和HO-1水平分别为(1.6±0.2)、(542.7±49.5)U/L和(17.1±2.3)U/L,显著高于妊娠结局良好组【分别为(1.2±0.3)、(515.3±41.8)U/L和(15.1±2.5)U/L,P<0.05】。结论 妊娠期DILI患者血清miR-21、Nrf2和HO-1水平显著升高,并随病情加重而升高,对临床判断病情有一定的帮助。

Objective The aim of this study was to explore serum microRNA-21(miR-21),nuclear factor-related factor 2(Nrf2)and heme oxygenase-1(HO-1)level changes in pregnant women with drug-induced liver injury(DILI).Methods 83 pregnant women with DILI and 58 healthy pregnant women who underwent obstetric examination at the same time were enrolled in our hospital between August 2017 and September 2021.Serum miR-21 was detected by real-time fluorescence PCR,and serum Nrf2 and HO-1 levels were measured by ELISA.Results The patients with DILI in our series included hepatocyte injury type in 53 cases,cholestasis type in 21 cases and mixed in 9 cases;based on the severity of liver injuries,it was found grade 1 in 31 cases,grade 2 in 32 cases,grade 3 in 16 cases and grade 4 in 4 cases;in our series,67 women had a very good pregnant outcomes,while in 16 women,the pregnant outcomes were not satisfied as showed with premature baby,dead fetus,and intrauterine fetal growth retardation;serum miR-21,Nrf2 and HO-1 levels in women with DILI were(1.5±0.2),(537.4±53.8)U/L and(16.7±3.1)U/L,significantly higher than[(0.4±0.1),(203.5±47.2)U/L and(11.4±2.2)U/L,respectively,P<0.05]healthy pregnant women;serum miR-21 and Nrf2 levels in women with cholestasis were(2.1±0.4)and(574.6±37.2)U/L,significantly higher than[(1.3±0.2)and(521.8±39.5)U/L,P<0.05]in women with hepatocyte injury or[(1.5±0.2)and(542.1±34.8)U/L,P<0.05]in women with mixed injury,and serum miR-21 level in women with mixed injury was much higher than in women with hepatocyte injury(P<0.05);serum miR-21,Nrf2 and HO-1 levels in women with grade 4 liver injury were(2.3±0.4),(589.0±35.1)U/L and(21.5±2.8)U/L,much higher than[(1.7±0.3),(573.2±38.6)U/L and(19.1±1.8)U/L,P<0.05]in women with grade 3,or[(1.5±0.3),(539.5±45.3)U/L and(16.4±2.5)U/L,P<0.05]in women with grade 2 or[(1.2±0.2),(503.7±41.0)U/L and(14.5±2.1)U/L,P<0.05]in women with grade 1 liver injury;serum miR-21,Nrf2 and HO-1 levels in pregnant women with unsatisfied outcomes were(1.6±0.2),(542.7±49.5)U/L and(17.1±2.3)U/L,all much higher than[(1.2±0.3),(515.3±41.8)U/L and(15.1±2.5)U/L,respectively,P<0.05]in women with normal outcomes.Conclusion Serum miR-21,Nrf2 and HO-1 levels in pregnant women with DILI increase greatly,which might be helpful in assessing the severity of liver injuries.