腺苷蛋氨酸联合糖皮质激素治疗胆汁淤积性肝病的临床效果及对血清Nrf2、Ho-1水平的影响

Clinical Effect of Ademetionine Combined with Glucocorticoid on Cholestatic Liver Disease and Its Influences on Serum Nrf2 and Ho-1 Levels

目的探讨腺苷蛋氨酸联合糖皮质激素治疗胆汁淤积性肝病(cholestatic liver disease,CLD)的临床效果及对血清核因子E2相关因子2(nuclear factor erythroid-2-related factor 2,Nrf2)、血红素氧合酶-1(heme oxygenase-1,Ho-1)水平的影响。方法选取2016年10月—2018年10月收治的94例CLD,根据治疗方法的不同,分为对照组与观察组,每组各47例。对照组予常规保肝治疗,观察组予常规保肝联合糖皮质激素治疗。两组均连续治疗4周。评估治疗后临床效果,记录治疗前后临床症状(疲乏、皮肤瘙痒、消化道症状及皮肤黄染)、肝功能相关指标[丙氨酸转氨酶(alanine aminotransferase,ALT)、碱性磷酸酶(alkaline phosphatase,ALP)、γ-谷氨酰转移酶(γ-glucosyltransferase,γ-GT)、总胆红素(total bilirubin,TBil)、总胆汁酸(total bile acid,TBA)及Ho-1]与Nrf2变化情况,观察治疗过程中不良反应发生情况。结果观察组治疗后总有效率明显高于对照组,比较差异有统计学意义(P<0.05)。与对照组治疗后比较,观察组治疗后疲乏、皮肤瘙痒、消化道症状、皮肤黄染的发生率明显下降,血清ALT、ALP、γ-GT、TBil及TBA水平下降,血清Ho-1、Nrf2水平升高,差异有统计学意义(P<0.05或P<0.01);与本组治疗前比较,两组治疗后疲乏、皮肤瘙痒、消化道症状、皮肤黄染的发生率降低,血清ALT、ALP、γ-GT、TBil及TBA水平降低,血清Ho-1、Nrf2水平升高,差异有统计学意义(P<0.05或P<0.01)。两组治疗过程中均未发生明显不良反应。结论腺苷蛋氨酸联合糖皮质激素治疗CLD可通过激活Nrf2/Ho-1通路,进而减轻患者临床症状,改善肝功能,效果显著,且安全性高。

Objective To explore the clinical effect of ademetionine combined with glucocorticoid on cholestatic liver disease(CLD)and its influences on levels of serum nuclear factor erythroid-2-related factor 2(Nrf2)and heme oxygenase-1(Ho-1).Methods A total of 94 CLD patients who were admitted during the period from October 2016 to October 2018 were enrolled.According to different treatment methods,they were divided into control group and observation group,with 47 cases in each group.The control group was given conventional liver protection treatment,while observation group was given conventional liver protection treatment and glucocorticoids.Both groups were consecutively treated for 4 weeks.The clinical effect after treatment was evaluated.The changes in clinical symptoms(fatigue,skin itching,gastrointestinal symptoms,yellowing skin),liver function-related indexes[alanine aminotransferase(ALT),alkaline phosphatase(ALP),γ-glutaminyl transferase(γ-GT),total bilirubin(TBil),total bile acid(TBA),Ho-1]and Nrf2 before and after treatment were recorded.The occurrence of adverse reactions during treatment was observed.Results The total response rate of treatment in observation group was significantly higher than that in control group(P<0.05).After treatment,the incidence of fatigue,skin itching,gastrointestinal symptoms and yellowing skin in observation group was significantly lower than that in control group,levels of serum ALT,ALP,γ-GT,TBil and TBA were lower than those in control group,while levels of serum Ho-1 and Nrf2 were higher than those in control group(P<0.05 or P<0.01).Compared with those before treatment,the incidence of fatigue,skin itching,gastrointestinal symptoms and yellowing skin was decreased,levels of serum ALT,ALP,γ-GT,TBil and TBA were decreased,while levels of Ho-1 and Nrf2 were increased in both groups(P<0.05 or P<0.01).There were no significant adverse reactions in either group during treatment.Conclusion Ademetionine combined with glucocorticoid in the treatment of CLD can alleviate clinical symptoms and improve liver function of patients by activating Nrf2/HO-1 pathway,with significant effects and higher safety.