甘草酸镁联合丁二磺酸腺苷蛋氨酸治疗药物性肝损伤患者疗效研究

Short-term efficacy of magnesium isoglycyrrhizinate and adenosylmethionine butanedisulfonate combination in treatment of patients with drug-induced liver injury

目的观察应用异甘草酸镁联合丁二磺酸腺苷蛋氨酸治疗药物性肝损伤(DILI)患者的疗效及血清血红素单加氧酶1(HO-1)、核因子E2相关因子2(Nrf-2)和谷胱甘肽过氧化物酶(GSH-Px)水平的变化。方法2018年1月~2019年12月我院收治的78例DILI患者,采用随机数字表法将患者分为对照组和联合组,各39例。给予对照组丁二磺酸腺苷蛋氨酸静脉滴注,联合组在此治疗的基础上予以异甘草酸镁注射液静脉滴注,两组均连续治疗2 w。采用免疫荧光法检测血清Nrf-2,采用ELISA法检测血清肿瘤坏死因子α(TNF-α)、白介素-10(IL-10)、一氧化氮(NO)、一氧化氮合成酶(NOS)、HO-1、GSH-Px和巨噬细胞移动抑制因子(MIF)水平。结果在治疗2周结束时,联合组血清丙氨酸氨基转移酶水平为(65.9±7.7)U/L,天门冬氨酸氨基转移酶水平为(58.5±7.3)U/L,血清总胆红素水平为(20.5±5.3)μmol/L,均显著低于对照组【分别为(93.5±11.2)U/L、(91.3±10.8)U/L和(25.2±7.9)μmol/L,P<0.05】;血清一氧化氮合酶水平为(47.7±5.8)U/mg,GSH-Px水平为(0.8±0.1)ng/mL,显著高于对照组【分别为(38.5±5.6)U/mg和(0.5±0.1)U/mg,P<0.05】,而血清HO-1水平为(0.4±0.1)ng/mL,Nrf-2水平为(0.5±0.1)ng/mL,显著低于对照组【分别为(0.7±0.1)ng/mL和(0.8±0.1)U/mg,P<0.05】;血清肿瘤坏死因子α水平为(3.0±0.5)ng/mL,MIF水平为(8.9±1.1)ng/mL,显著低于对照组【分别为(4.2±0.6)ng/mL和(11.4±1.5)ng/mL,P<0.05】,而血清血清白介素-10水平为(33.1±4.4)pg/mL,NO水平为(66.5±7.3)μmol/L,显著高于对照组【分别为(22.5±2.9)pg/mL和(41.1±5.6)μmol/L,P<0.05】。结论应用异甘草酸镁联合丁二磺酸腺苷蛋氨酸治疗DILI患者疗效较好,可能与其抑制了炎症反应,提高了抗氧化能力有关。

Objective The aim of this study was to investigate the short-term efficacy of magnesium isoglycyrrhizinate and adenosylmethionine butanedisulfonate combination in treatment of patients with drug-induced liver injury(DILI)and serum heme monooxygenase 1(HO-1),nuclear factor E2 related factor 2(Nrf-2)and glutathione peroxidase(GSH-Px)level changes.Methods 78 patients with DILI were enrolled in this study between January 2018 and December 2019,and were randomly divided into control and combination groups,with 39 cases in each group.The patients in control group received intravenous infusion of adenosylmethionine butanedisulfonate,and those in the combination received intravenous infusion of magnesium isoglycyrrhizinate at the base of medicine in the control for two weeks.Serum Nrf-2,TNF-α,IL-10,NO,NOS,HO-1,GSH-Px and macrophage dectected.Results At the end two week migration inhibitory factor(MIF)were of treatment,serum alanine aminotransaminase level in the combination group was(65.9±7.7)U/L,serum AST level was(58.5±7.3)U/L,and serum total bilirubin level was(20.5±5.3)μmol/L,all significantly lower than【(93.5±11.2)U/L,(91.3±10.8)U/L and(25.2±7.9)μmol/L,respectively,P<0.05】in the control;serum NOS level was(47.7±5.8)U/mg,and serum GSH-Px level was(0.8±0.1)ng/mL,both significantly higher than【(38.5±5.6)U/mg and(0.5±0.1)U/mg,respectively,P<0.05】,while serum HO-1 level was(0.4±0.1)ng/mL,and serum Nrf-2 level was(0.5±0.1)ng/mL,both significantly lower than【(0.7±0.1)ng/mL and(0.8±0.1)U/mg,respectively,P<0.05】in the control;serum TNF-αlevel was(3.0±0.5)ng/mL,and serum MIF level was(8.9±1.1)ng/mL,significantly lower than【(4.2±0.6)ng/mL and(11.4±1.5)ng/mL,respectively,P<0.05】,while serum IL-10 level was(33.1±4.4)pg/mL,and serum NO level was(66.5±7.3)μmol/L,significantly higher than【(22.5±2.9)pg/mL and(41.1±5.6)μmol/L,respectively,P<0.05】in the control.Conclusion The magnesium isoglycyrrhizinate and adenosylmethionine butanedisulfonate combination in the treatment of patients with DILI have a short-term efficacy,which might be related to the inhibition of inflammatory and oxidative stress reactions,and needs further clinical investigation.