地塞米松对双氯芬酸钠肝损伤的保护作用

目的探讨地塞米松(dexamethasone,Dex)对双氯芬酸钠诱导的大鼠药物性肝损伤的保护作用及部分机制。方法大鼠随机分为正常对照组、模型对照组、Dex(10 mg.kg-1)给药组。Dex(10 mg.kg-1)腹腔注射,1 h后腹腔注射双氯芬酸钠100 mg.kg-1,24 h后检测ALT和AST活性、测定肝匀浆中MDA、GSH含量和GSH-Px、SOD活性,观察肝组织病理学变化,并测肝线粒体膜电位、线粒体肿胀度、NADH水平、SDH及ATPase活性。结果模型对照组血清ALT、AST升高,光镜下可见肝小叶内肝细胞片状坏死,肝匀浆MDA含量升高,GSH、GSH-Px和SOD含量降低,肝线粒体NADH含量、SDH及ATPase活性降低。Dex可明显降低ALT、AST活性(P<0.05),减轻肝脏炎症,降低肝匀浆中MDA含量(P<0.01),升高GSH含量、GSH-Px和SOD活性以及线粒体中NADH含量、SDH及ATPase活性(P<0.01)。结论 Dex对双氯芬酸钠诱导的大鼠药物性肝损伤有保护作用,作用机制可能与减轻线粒体损伤有关。

Protective effects of dexamethasone on acute liver injury induced by diclofenac

Aim To investigate the effect of dexamethasone(Dex)on acute liver injury induced by diclofenac(Dcf)in rats.Methods SD rats were randomly divided into control group,Dcf group,and Dex group.Liver injury was induced by administrated intraperitoneally with Dcf 100 mg·kg-1 in rats,Dex(10 mg·kg-1)was treated intraperitoneally 1 h before Dcf administration.The alanine aminotransferase(ALT)and aspartate aminotransferase(AST) values were analyzed,liver tissue slices were prepared for pathology evaluation,and the manganese-superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px) activity,the malonicdialdehyde(MDA) and glutathion(GSH) content in liver tissue were also determined.The mito-chondria function parameters(mitochondrial swelling and mitochondrial membrane potential,mitochondrial ATPase and SDH activity) were assessed in vivo.Results Compared with Dcf group,the ALT and AST levels were significantly decreased in Dex group which was accompanied with the reduced liver cellular damage.Dexamethasone decreased MDA contents in liver tissue,whereas the content of SOD,GSH and GSH-Px was increased in liver tissue.Further,Dexamethasone inhibited Dcf-induced liver mitochondrial dysfunction in rats,enhanced the activity of ATPase and SDH and helped to maintain a normal balance of energy metabolism.Conclusion Dcf-induced liver injury can be inhibited by Dex effectively,and its mechanism may be associated with the protection on mitochondrial function.