FK866在对乙酰氨基酚诱导的急性肝损伤中的 保护作用及机制研究

Protective effect of FK866 on acute liver injury induced by acetaminophen and its mechanism

摘要:

目的：探讨FK866在对乙酰氨基酚（acetaminophen，APAP）诱导小鼠急性肝损伤（acute liver injury，ALI）中的保护作用及机制。方法：24只6周龄的雄性C57BL/6小鼠随机分为对照组、FK866组、APAP组、FK866加APAP组。通过比色法检测血清中丙氨酸转氨酶（alanine aminotransferase，ALT）、天冬氨酸转氨酸（aspartate aminotransferase，AST）活性；HE染色观察肝组织病理学变化；酶联免疫法检测血清中白细胞介素（interleukin，IL）-6、IL-1β、肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）含量；Western blot检测尼克酰胺磷酸核糖转移酶（nicotinamide phosphoribosyl-tiansferase，NAMPT）的蛋白表达水平。结果：FK866加APAP组中，ALT和AST分别为（13.969±0.290）、（7.150±0.669） IU/L，较APAP组明显降低（ALT：F=364.709，P=0.000；AST：F=130.398，P=0.000），可见肝脏组织小叶结构较清晰，细胞变性轻微，无明显淤血；炎症因子IL-6、IL-1β、TNF-α检测值分别为（176.333±0.775）、（79.765±1.000）、（147.083±1.000） pg/mL，较APAP组含量明显减少（IL-6：F=207.106，P=0.000；IL-1β：F=165.027，P=0.000；TNF-α：F=118.636，P=0.000）；NAMPT蛋白表达水平较APAP组下调。结论：FK866在APAP诱导的ALI中对肝脏具有保护作用，其机制可能与抗炎效应相关。

Abstract:

Objective：To investigate the protective effect of FK866 on acute liver injury（ALI） induced by acetaminophen（APAP） and its mechanism. Methods：Twenty-four male C57BL/6 mice（6-week-old） were randomly divided into the control group，FK866 group，APAP group and FK866+APAP group. The activities of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum were determined by colorimetric method，the pathological changes of liver by HE（hematoxylin eosin） staining，the levels of tu－mor necrosis factor-α（TNF-α），interleukin-6（IL-6） and interleukin-1β（IL-1β） by ELISA，and the expression of nicotinamide phosphoribosyltransferase（NAMPT） by Western blot. Results：In the FK866+APAP group，the serum activities of ALT and AST were （13.969±0.290） and （7.150±0.669） IU/L respectively and significantly lower than those of the APAP group（ALT：F=364.709，P=0.000；AST：F=130.398，P=0.000）. The lobular structure was clear，the cell degeneration was mild，and no obvious congestion was observed in FK866-treated group. Furthermore，the serum levels of IL-6，IL-1β and TNF-α were （176.333±0.775），（79.765±1.000） and （147.083±1.000） pg/mL respectively，indicating the inflammatory factors were notably inhibited by FK866（F=207.106，P=0.000；F=165.027，P=0.000；F=118.636，P=0.000）. The expression of NAMPT protein was also down-regulated. Conclusion：FK866 can protect against the acute liver injury induced by APAP，and the anti-inflammatory effects may be involved in it.