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

作　　者：蒋师放 陈倩竹[2] 马磊 范克瑞 胡凯 陈益[3] 许娟娟 姜蓉[3] 李龙江 Jiang Shifan;Chen Qianzhu;Ma Lei;Fan Kerui;Hu Kai;Chen Yi;Xu Juanjuan;Jiang Rong;Li Longjiang(Teaching and Research Section of Pathophysiology ,Laboratory of Stem Cell and Tissue Engineering,College of Basic Medicine,Chongqing Medical University;Department of Orthopedics,The First Affiliated Hospital of Chongqing Medical University;Teaching and Research Section of Histology and Embryology,Laboratory of Stem Cell and Tissue Engineering,College of Basic Medicine,Chongqing Medical University)

机构地区：[1]重庆医科大学基础医学院病理生理学教研室重庆医科大学干细胞与组织工程研究室,重庆400016 [2]重庆医科大学附属第一医院骨科,重庆400016 [3]重庆医科大学基础医学院组织胚胎学教研室重庆医科大学干细胞与组织工程研究室,重庆400016

出　　处：《重庆医科大学学报》2018年第11期1433-1436,共4页Journal of Chongqing Medical University

基　　金：重庆市渝中区科委科技计划资助项目(编号:20150119)

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。Objective :To investigate the protective effect of FK866on acute liver injury (ALI)induced by acetaminophen (APAP )and its mechanism.Methods:Twenty-four male C57BL/6mice(6-week-old)were randomly divided into the control group,FK866group, 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 tumor 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.

关 键 词：FK866 对乙酰氨基酚 急性肝损伤 

分 类 号：R99[医药卫生—毒理学]