SKLB-102对ConA诱导的小鼠急性肝炎治疗研究

SKLB-102 Inhibits Acute Hepatitis Induced by Concanavalin A in Mice

目的研究5-(4-甲氧基苯亚甲基)-2-硫代-二氢嘧啶-4,6(1H,5H)-二酮(SKLB-102)对小鼠急性肝炎的治疗效果。方法体外巨噬细胞趋化抑制实验,检测SKLB-102对巨噬细胞趋化的抑制作用;建立刀豆蛋白A(ConA)诱导的小鼠急性肝炎模型,并在造模后给予SKLB-102进行治疗干预。采用临床自动生化分析检测ALT、AST变化;ELISA检测血清中肿瘤坏死因子(TNF-α)含量;HE染色组织病理学观察,评价SKLB-102治疗效果。结果体外巨噬细胞迁移实验显示,SKLB-102能明显抑制MCP-1诱导的RAW264.7细胞迁移;体内抗急性肝炎效果研究证明,SKLB-102降低ConA诱导急性肝炎模型小鼠血清AST、ALT含量,下调TNF-α表达;组织病理学显示SKLB-102明显减轻急性肝炎小鼠的肝组织损伤及炎性细胞浸润。结论SKLB-102体外具有明显抑制巨噬细胞趋化作用,体内显示很好的抑制TNF-α产生和治疗急性肝炎效果。SKLB-102治疗急性肝炎效果可能与其抑制免疫细胞趋化和炎性细胞因子产生有关。

Objective To test the effect of 5-（4-methoxybenzylidene）-2-thioxo-dihydropyrimidine-4,6 （1H, 5H）-dione（SKLB-102） on acute hepatic inflammatory induced by concanavalin A （ConA） in mice. Methods The inhibitive effect of SKLB-102 on RAW264. 7 cell migration induced by recombinant rat monocyte chemotactic protein-1 （MCP-1） was tested. The serum from the ConA-treated mice was collected after intragastric administration of SKLB-102 at the dose of 50 mg/kg bodyweight. The serum AST and ALT were determined by an automatic analyzer, and the serum TNF-α was determined with enzyme-linked immunosorbent assay （ELISA） kits. The liver samples were fixed in 10% formalin, embedded in paraffin, sectioned and then stained with hematoxylin and eosin for histological examinations. Results SKLB-102 markedly reduced cell migrations, successfully reduced serum AST, ALT and down-regulated TNF-α. Conclusion SKLB-102 is likely to suppress the occurrence of Con Ainduced hepatitis by suppressing macrophages migration and TNF- α releases.