Caspase抑制剂F1013对刀豆蛋白A诱导小鼠急性肝损伤的治疗作用

目的研究Caspase抑制剂F1013对刀豆蛋白A(Co-nA)所致小鼠急性肝损伤模型的治疗作用,并对其机制进行初步探讨。方法 60只♂BALB/c小鼠随机分成对照组、模型组、阳性药组(NAC 155 mg.kg-1)和F1013(5,2.5,1.25 mg.kg-1)给药组。除对照组外,其余组小鼠均尾静脉注射ConA建立小鼠急性肝损伤模型,造模后2 h,阳性药组腹腔注射NAC,F1013给药组和模型组分别皮下注射F1013和溶媒。造模后8 h留取血清检测丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、总胆红素(T-Bil)含量和TNF-α水平,肝组织进行HE染色,并检测肝细胞凋亡率。结果在Co-nA诱导小鼠急性肝损伤模型,F1013组均明显改善肝脏病理组织损伤;明显降低血清ALT、AST、T-Bil和TNF-α水平及肝细胞凋亡率(P<0.01或P<0.05)。结论 F1013对Co-nA所致小鼠急性肝损伤具有较好的治疗作用,其机制可能与减少TNF-α的产生及抗肝细胞凋亡有关。

Therapeutical effect of the caspase selective inhibitor F1013 on ConA-induced acute hepatic injury in mice

Aim To investigate the therapeutical effect and the mechanism of F1013 on acute hepatic injury(AHI) of mice induced by concanavalin A(ConA).Methods 60 male BALB/c mice were randomly divided into groups,and were intravenously(iv) injected with ConA to induce AHI.2 hours later,N-acetylc-steine(NAC) was intraperitoneally(ip) injected,and F1013 or solvent was subcutaneously(sc) injected.8 hours after ConA injection,a single liver segment and blood were taken for the histological analysis and the detection of hepatocellular apoptosis,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(T-Bil) and tumor necrosis factor-α(TNF-α).Results F1013(5,2.5,1.25 mg·kg-1) effectively improved the live lesion,and markedly decreased the elevated serum levels of ALT,AST,T-Bil,TNF-α and inhibited hepatocyte apoptosis.Conclusions F1013 has a therapeutical effect on mice with AIH induced by ConA.This might be associated with reducing TNF-α level and the inhibition of cell apoptosis in liver tissue.