NF-B、Bcl-2在大鼠非酒精性肝病肝细胞凋亡中的作用  

Role of NF-κB and Bcl-2 in hepatocyte apoptosis in rats with NAFLD

作　　者：石海燕[1] 李珏宏 李昌平[3] 康敏[3] 钟晓琳[3] 

机构地区：[1]四川省巴中市中心医院,四川省巴中市636000 [2]四川大学华西临床医学院,四川省成都市610041 [3]泸州医学院附属医院,四川省泸州市646000

出　　处：《世界华人消化杂志》2013年第20期1955-1960,共6页World Chinese Journal of Digestology

基　　金：2011年泸州市科技局基金资助项目;No.2011-I-S39(2/6)~~

摘　　要：目的:通过核因子B(nuclear factor κB,NF-κB)、Bcl-2在大鼠非酒精性肝病(non-alcoholic fatty liver disease,NAFLD)中的表达,研究线粒体损伤途径在肝细胞凋亡中的作用及NAFLD的发病机制.方法:将36只SD大鼠随机分为正常组18只,模型组18只,分别于6、10、14wk处死各组大鼠,6只在光镜下观察肝组织病理学形态;血浆肿瘤坏死因子-(tumor necrosis factor-α,TNF-α)采用放免法测定;TUNNEL法测肝细胞凋亡百分数;免疫组织化学检测Bcl-2、NF-B蛋白在肝细胞中的表达情况.结果:肝组织病理结果提示正常组肝组织结构正常,模型组第6、10、14周大鼠肝小叶脂肪变性,门管区及周围及腺泡第10、14周大鼠可见炎性细胞浸润,第14周大鼠出现胶原纤维生成.细胞凋亡百分数结果提示正常组在各时间段有散在凋亡阳性表现,模型组凋亡细胞表达明显高于正常组,且随时间的延长表达逐渐增多.免疫组织化学结果显示造模组随时间的延长Bcl-2表达逐步增加,且脂肪变明显的区域阳性染色细胞较相对正常肝细胞染色深.NF-B定位于细胞质和/或细胞核,模型组第6、10、14周大鼠肝细胞内可见NF-B明显活化,而且随造模时间延长,其表达随之增多.各组大鼠血浆TNF-测定模型组各组大鼠血浆TNF-α表达随着造模时间的延长逐渐增高,且均高于同时间段正常组表达.结论:细胞凋亡是NAFLD病情进展的重要阶段,NF-κB、Bcl-2在NAFLD肝细胞凋亡中起到重要作用.AIM：To examine the expression of nuclear factor B（NF-κB） and Bcl-2 in non-alcoholic fatty liver disease（NAFLD） in rats and to investigate the role of the mitochondrial injury pathway in hepatocyte apoptosis and the pathogenesis of NAFLD.METHODS：Thirty-six rats were randomly and equally divided into two groups：a control group and an experimental group.The rats were killed at weeks 6,10,and 14,and histopathological features of the liver were observed by microscopy.Plasma levels of tumor necrosis factor-α（TNF-α）were measured by radioimmunoassay,hepatocyte apoptosis was assessed by TUNNEL assay,and expression of Bcl-2 and NF-κB proteins in hepatocytes was measured by immunohistochemistry.RESULTS：Histopathological staining showed the liver structure was normal in the control group.However,lobular steatosis was observed in the model group.Portal and periportal inflammation and lobular inflammation were noted at week 10,and liver fibrosis was visible at week 14.Compared to the control group,apoptosis was increased in the model group,and this process was time-dependent.A time-dependent increase in the expression of Bcl-2 and NF-κB in liver tissue and serum levels of TNF-αwas also found in the model group compared to the control group.CONCLUSION：Apoptosis is a critical step for the development of NAFLD,and NF-κB and Bcl-2 play an important role in hepatocyte apoptosis in NAFLD.

关 键 词：非酒精性脂肪性肝病 肝细胞凋亡 核因子B BCL-2 肿瘤坏死因子-Α 

分 类 号：R575.5[医药卫生—消化系统]