关键词: 药物性肝损伤, 微小RNA-21, 核因子相关因子2, 血红素氧合酶-1, 临床意义, 妊娠

Abstract: 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.

Key words: Drug-induced liver injury, MicroRNA-21, Nuclear factor-related factor 2, Heme oxygenase-1, Clinical implications, Pregnancy