肿瘤坏死因子α对急性肝功能衰竭小鼠中血脑屏障紧密连接的影响及机制  

Impact and Mechanisms of Tumor Necrosis Factor-α on the Blood-brain Barrier Tight Junction in Acute Liver Failure Mice

作　　者：韩家峰[1] 吕飒[1] 王文[1] 刘沛[1] 

机构地区：[1]中国医科大学附属第一医院传染科,沈阳110001

出　　处：《中国医科大学学报》2012年第9期776-779,共4页Journal of China Medical University

基　　金：国家自然科学基金资助项目(97100252)

摘　　要：目的探讨急性肝功能衰竭中肿瘤坏死因子α(TNF-α)对血脑屏障(BBB)渗透性的影响。方法通过施加D-氨基半路糖(D-GalN)和脂多糖或D-GalN和TNF-α形成急性肝功能衰竭小鼠模型。通过依文思蓝染色研究BBB的渗透性,并在电镜下观察其形态改变。Western blot检测Occludin蛋白的表达。结果在急性肝功能衰竭小鼠中BBB渗透性增加,电镜下观察到组织的紧密连接瓦解和内皮细胞皱缩,并伴随囊泡和空泡增加。此外,急性肝功能衰竭小鼠的脑组织紧密连接相关蛋白Occludin的表达显著降低。结论 TNF-α在急性肝功能衰竭小鼠脑水肿中的形成过程中起到重要的作用,BBB渗透性增加可能是由于紧密连接丧失和其相关蛋白Occludin下调所致。Objective To investigate the mechanism of tumor necrosis factor-α（TNF-α）in changing the permeability of the blood-brain barrier（BBB）during acute liver failure（ALF）.Methods ALF rat models were established by administering D-galactosamine（D-GalN） and TNF-α.We tried to investigate the BBB permeability with method of Evas blue（EB）staining and detect the BBB structure using electron microscopy.Expressions of TJ-associated protein occludin protein were determined by Western blot.Results Increased BBB permeability in ALF mice was found in ALF rats.Tight junction（TJ）disruption and EC shrinkage with increased vesicles and vacuoles were detected in the model.In addition,the expression of occludin was markedly reduced in the model.Conclusion Our results suggested that TNF-α plays a critical role in the development of brain edema in ALF rats.Increased BBB permeability might attribute to the disruption of TJs,and the reduction of occludin expression.

关 键 词：急性肝功能衰竭 肿瘤坏死因子Α 紧密连接 

分 类 号：R575.3[医药卫生—消化系统]