α-硫辛酸在Graves'病合并肝损伤中的保护作用及机制研究

Protective Effects and Mechanism of α-lipoic Acid in Graves' Disease Complicated with Liver Damage

背景Graves'病(GD)患者发生肝损害常见,少数甚至出现肝衰竭。GD导致肝损伤的机制尚不明确。现有研究发现甲状腺激素可诱导大鼠肝脏的氧化应激。α-硫辛酸(ALA)具有抗氧化应激作用。目的探讨ALA在GD合并肝损伤中的保护作用及机制。方法选取2015年5月—2016年12月在锦州医科大学附属第三医院门诊初诊为GD合并肝损伤或GD合并肝损伤治愈1年后复发者共90例,采用随机数字法将患者分为常规组、激素组、ALA组,各30例。常规组给予复方二氯醋酸二异丙胺、水飞蓟宾胶囊联合甲巯咪唑治疗,激素组在常规组的基础上给予甲泼尼龙治疗,ALA组在常规组的基础上给予ALA治疗。分别于治疗前和治疗第14天、第28天检测丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST);分别于治疗前、治疗第28天检测游离三碘甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)、甲状腺球蛋白抗体(TgAb)、甲状腺过氧化物酶抗体(TPOAb)、超氧化物歧化酶(SOD)、丙二醛(MDA)和总抗氧化能力(T-AOC)。结果 3组第14天、第28天的ALT、AST均低于治疗前(P<0.01);激素组、ALA组第14、28天的ALT、AST均低于常规组,激素组第28天的ALT、AST均低于ALA组(P<0.01)。3组第28天的TSH水平均高于治疗前,FT3、FT4、TgAb、TPOAb水平均低于治疗前(P<0.01);其中,激素组、ALA组第28天的TSH水平高于常规组,ALA组第28天的TSH水平低于激素组,激素组第28天FT3、TgAb、TPOAb水平低于常规组、ALA组(P<0.01)。3组第28天的SOD、T-AOC水平均高于治疗前,MDA水平均低于治疗前(P<0.01);激素组、ALA组第28天的SOD、T-AOC水平均高于常规组,MDA水平均低于常规组(P<0.01);激素组第28天的SOD、T-AOC水平均高于ALA组,MDA水平低于ALA组(P<0.01)。结论 ALA可通过减弱GD患者的氧化应激反应,从而减少肝损伤。

Background Liver damage is common in patients with Graves’ disease(GD),and a few of them even have liver failure.The mechanism of GD-induced liver injury remains unclear. Existing studies have found that thyroid hormone can induce oxidative stress in rat liver,and α-lipoic acid(ALA)has the effect of anti-oxidative stress. ObjectiveTo investigate the protective effects and mechanism of ALA in GD complicated with liver damage.Methods A total of 90 patients who first diagnosed as GD combined with liver damage or had recurrence after one year of initial diagnosis with GD combined with liver damage in the Third Affiliated Hospital of Jinzhou Medical University between May 2015 and December 2016 were selected and divided into three groups:conventional group,hormone group and ALA group,each with 30 cases.Conventional group was given compound diisopropylamine dichloroacetate,silybin capsule combined with methimazole treatment.Hormone group was given methylprednisolone treatment on the basis of treatment in conventional group.ALA group was given ALA treatment on the basis of treatment in conventional group.Alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected before treatment and on the 14 th and 28 th day after treatment;free triiodothyronine(FT3),free thyroxine(FT4),thyroid stimulating hormone(TSH),thyroglobulin antibody(TgAb),thyroid peroxidase antibody(TPOAb),superoxide dismutase(SOD),malondialdehyde(MDA) and total antioxidant capacity(T-AOC) were detected before treatment and on the 28 th day after treatment.Results ALT and AST on the 14 th and 28 th day of treatment in three groups were lower than those before treatment(P<0.01).The ALT and AST on the 14 th and 28 th day of treatment in hormone group and ALA group were lower than those in conventional group(P<0.01).The ALT and AST of hormone group on the 28 th day of treatment were lower than those of ALA group(P<0.01).TSH level on the 28 th day of treatment in three groups were higher than those before treatment,and FT3,FT4,TgAb and TPOAb levels were lower than those before treatment(P<0.01);TSH level in hormone group and ALA group was higher than that in conventional group on the 28 th day,TSH level in ALA group was lower than that in hormone group on the 28 th day,FT3,TgAb,TPOAb level in hormone group was lower than that in conventional group and ALA group on the 28 th day(P<0.01).SOD and T-AOC levels on the 28 th day of the three groups were higher than those before treatment(P<0.01),and MDA level was lower than that before treatment(P<0.01).The levels of serum SOD and T-AOC on the 28 th day of treatment in hormone group and ALA group were higher than those in conventional group,and MDA was lower than that in conventional group;the levels of SOD and T-AOC on the 28 th day of treatment in hormone group were higher than those in ALA group,and MDA level was lower than that in ALA group(P<0.01).Conclusion ALA have a protective effect on liver damage by reducing oxidative stress in patients with GD.