注射用谷胱甘肽联合硫普罗宁治疗药物性肝损伤患者疗效研究

Combination of glutathione and tiopronin in the treatment of patients with drug-induced liver injury

目的探讨应用注射用谷胱甘肽联合硫普罗宁治疗药物性肝损伤(DILI)患者的疗效。方法2019年12月~2022年8月我院诊治的DILI患者72例,被随机分为对照组36例和观察组36例,分别给予硫普罗宁治疗或谷胱甘肽联合硫普罗宁治疗2~4 w。采用黄嘌呤氧化法检测血清超氧化物歧化酶(SOD)水平,采用硫代巴比妥酸法检测血清丙二醛(MDA)水平,采用二硫基双硝基苯甲酸法检测血清谷胱甘肽过氧化物酶(GSH-Px)水平,采用ELISA法检测血清人血红素氧合酶1(HO-1)、白细胞介素-6(IL-6)、C反应蛋白(CRP)、肿瘤坏死因子α(TNF-α)和IL-1β水平。结果在治疗4周末,观察组血清ALT和AST水平分别为(40.6±11.5)U/L和(31.0±2.6)U/L,显著低于对照组【分别为(64.6±13.9)U/L和(63.7±15.3)U/L,P<0.05】,而两组血清总胆红素和GGT水平无显著性相差【分别为(16.8±3.9)μmol/L和(59.2±13.3)U/L对(20.2±4.2)μmol/L和(60.8±14.7)U/L,P>0.05】;观察组血清SOD、GSH-Px和HO-1水平分别为(82.4±12.7)U/L、(99.8±16.6)U/L和(256.7±20.8)U/L,显著高于对照组【分别为(75.6±10.9)U/L、(80.6±15.4)U/L和(197.5±24.9)U/L,P<0.05】,而血清MDA水平为(5.1±0.8)μmol/L,显著低于对照组【(6.2±1.3)μmol/L,P<0.05】;观察组血清IL-6、TNF-α、IL-1β和CRP水平分别为(5.1±1.7)pg/mL、(4.4±1.7)pg/mL、(11.2±4.1)ng/mL和(3.9±2.0)mg/L,均显著低于对照组【分别为(9.7±1.1)pg/mL、(10.2±1.8)pg/mL、(25.3±4.8)ng/mL和(13.6±2.9)mg/L,P<0.05】。结论应用注射用谷胱甘肽联合硫普罗宁治疗DILI患者可有效改善肝功能水平,可能与其抑制了机体炎症和氧化应激反应有关,值得临床进一步观察。

Objective The aim of this study was to observe the combination of glutathione and tiopronin in the treatment of patients with drug-induced liver injury(DILI).Methods 72 patients with DILI were enrolled in our hospital between December 2019 and August 2022,and were randomly divided into control(n=36)and observation(n=36)group,receiving tiopronin alone or tiopronin and glutathione combination treatment for two to four weeks.Serum malondialdehyde(MDA),superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)were detected by thibabituric acid,xanthine oxidation or dithiobis-nitrobenzoic acid methods,respectively.Serum human heme oxygenase-1(HO-1),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),IL-1βand C-reactive protein(CRP)levels were detected by ELISA.Results At the end of treatment,serum ALT and AST levels in the observation group were(40.6±11.5)U/L and(31.0±2.6)U/L,both significantly lower than[(64.6±13.9)U/L and(63.7±15.3)U/L,respectively,P<0.05]in the control,while there were no significant differences respect to serum bilirubin and GGT levels in the two groups[(16.8±3.9)μmol/L and(59.2±13.3)U/L vs.(20.2±4.2)μmol/L and(60.8±14.7)U/L,respectively,P>0.05];serum SOD,GSH-Px and HO-1 levels in the observation group were(82.4±12.7)U/L,(99.8±16.6)U/L and(256.7±20.8)U/L,all significantly higher than[(75.6±10.9)U/L,(80.6±15.4)U/L and(197.5±24.9)U/L,respectively,P<0.05],while serum MDA level was(5.1±0.8)μmol/L,much lower than[(6.2±1.3)μmol/L,P<0.05]in the control;serum IL-6,TNF-α,IL-1βand CRP levels were(5.1±1.7)pg/mL,(4.4±1.7)pg/mL,(11.2±4.1)ng/mL and(3.9±2.0)mg/L,all significantly lower than[(9.7±1.1)pg/mL,(10.2±1.8)pg/mL,(25.3±4.8)ng/mL and(13.6±2.9)mg/L,respectively,P<0.05]in the control group.Conclusion The combination of glutathione and tiopronin in the treatment of patients with DILI could effectively improve liver function tests back to normal,which might alleviate body inflammatory and oxidative stress reactions,and warrants further clinical investigation.