熊去氧胆酸联合S-腺苷蛋氨酸对药物性肝损伤患者肝功能、Nrf2抗氧化、炎症反应的影响

Influence of ursodeoxycholic acid combined with s-adenosine methionine on liver function,Nrf2 antioxidant and inflammatory response in patients with drug-induced liver injury

目的研究熊去氧胆酸联合S-腺苷蛋氨酸对药物性肝损伤患者肝功能、Nrf2抗氧化、炎症反应的影响。方法前瞻性选择2014年3月至2017年12月期间在上海市东方医院诊断为药物性肝损伤的患者作为研究对象,随机分为接受熊去氧胆酸联合S-腺苷蛋氨酸治疗的联合组、接受S-腺苷蛋氨酸治疗的对照组。分别于治疗前、治疗后6周、12周,测定机体血清肝功能[总胆红素(TBi L)、血丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]指标、炎症反应指标[一氧化氮合酶(NOS)、肿瘤坏死因子α(TNF-α)、血骨桥蛋白(OPN)、血清中巨噬细胞移动抑制因子(MIF)、白细胞介素-10(IL-10)、血浆可溶性肿瘤坏死因子受体1(s TNFR1)、一氧化氮(NO)]的含量以及外周血中Nrf2抗氧化指标[Kelch样ECH相关蛋白1(Keap1)、核因子E2相关因子(Nrf-2)、醌NADH脱氢酶1(NQO1)、血红素氧合酶1(HO1)、谷胱甘肽过氧化物酶(GSH-Px)]的表达量。结果与组内治疗前比较,组内治疗后血清中TBi L、ALT、AST、NOS、TNF-α、OPN、MIF、NO的含量以及外周血中Nrf-2、NQO1、HO1、GSH-Px的表达强度均显著降低,外周血中Keap1的表达强度以及血清中IL-10、s TNFR1的含量均显著升高,且联合组治疗后血清中TBi L、ALT、AST、NOS、TNF-α、OPN、MIF、NO的含量以及外周血中Nrf-2、NQO1、HO1、GSH-Px的表达强度低于对照组,外周血中Keap1的表达强度以及血清中IL-10、s TNFR1的含量高于对照组。结论熊去氧胆酸联合S-腺苷蛋氨酸用于药物性肝损伤的治疗能够改善肝功能、抑制Nrf2抗氧化通路以及炎症反应的过度激活。

Objective To study the influence of ursodeoxycholic acid combined with s-adenosine methionine on liver function,Nrf2 antioxidant and inflammatory response in patients with drug-induced liver injury.Methods Patients diagnosed with drug-induced liver injury in Shanghai Oriental hospital from March 2014 to December 2017 were randomly divided into the group receiving ursodeoxycholic acid combined with s-adenosine methionine treatment and the control group receiving s-adenosine methionine treatment.Before and after treatment,6 weeks and 12weeks,serum liver function,inflammatory response and Nrf2 expression in peripheral blood were measured.Results Compared with that before treatment in the group,the contents of TBiL,ALT,AST,NOS,TNF-α,OPN,MIF and NO,as well as the expression intensity of nrf-2,NQO1,HO1 and gsh-px in the serum were significantly decreased after treatment.Keap1 expression intensity in peripheral blood and the content of serum IL-10,sTNFR1 joint group after treatment were significantly higher and the serum TBiL,ALT,AST,NOS,TNF-α,OPN,MIF,the content of NO and peripheral blood in the Nrf-2,NQO1,the expression of HO1 and gsh-px strength were lower than the control group,the peripheral blood of Keap1 expression of strength and the content of serum IL-10,sTNFR1 were higher than the control group.Conclusion ursodeoxycholic acid combined with s-adenosine methionine in the treatment of drug-induced liver injury can improve liver function,inhibit the Nrf2 antioxidant pathway and over-activate the inflammatory response.