急性肝衰竭小鼠血清TNFα与血脑屏障通透性的改变  

Changes of Serum Tumor Necrosis Factor-α Level and Blood-brain Barrier Permeability in Mice with Acute Liver Failure

作　　者：王文[1] 吕飒[2] 周莹[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 [2]北京302医院生物治疗研究中心,北京100039

出　　处：《中国医科大学学报》2011年第8期681-683,共3页Journal of China Medical University

基　　金：国家自然科学基金资助项目(30670947)

摘　　要：目的探讨对乙酰氨基酚/扑热息痛(APAP)导致的急性肝衰竭(ALF)小鼠模型中血清肿瘤坏死因子α(TNFα)及血脑屏障(BBB)通透性的改变。方法应用APAP建立ALF小鼠模型,观察死亡率、血清丙氨酸氨基转移酶(ALT)及TNFα含量及肝组织病理学变化。利用伊文思蓝(EB)在脑中含量检测BBB通透性。结果小鼠注射APAP后4 h开始死亡,6 h死亡率达到高峰。血清ALT水平2 h开始升高,9 h达到高峰。肝脏病理学9 h病变最重,表现为大块或亚大块出血性坏死。6 h组血清TNFα较0小时组显著升高。脑组织EB含量于2 h开始升高,6 h达到高峰。结论在APAP所致的ALF动物模型中,血清TNFα水平明显增高,且与脑组织EB含量的显著升高相一致。TNFα可能是导致ALF时BBB通透性增加的重要细胞因子。Objective To investigate the changes of serum tumor necrosis factor（TNF）α level and the blood-brain barrier（BBB） permeability in acetaminophen（APAP）-induced ALF.Methods Acetaminophen was used to induce acute liver failure of male Balb/c mice.Serum levels of alanine transaminase（ALT） and TNFα were determined.The liver tissues were fixed for histopathologic analysis.The permeability of BBB was detected by Evans blue staining（EB）.Results The mice began to die 4 h after injection of APAP and the mortality rate reached 25% at 6 h.The serum levels of ALT began to increase at 2 h,and reached the peak at 9 h,which was consistent with the changes of liver histopathology,showing massive or submassive necrosis.The level of serum TNFα was significantly increased at 6 h.The concentration of EB in brain tissue also reached the peak at 6 h.Conclusion In APAP-induced ALF,serum TNFα level was obviously increased,which was consistent with the increased concentration of EB in brain tissue.TNFα might be an important cytokine that increased the permeability of BBB in APAP-induced ALF.

关 键 词：急性肝衰竭 肿瘤坏死因子 血脑屏障 

分 类 号：R575.1[医药卫生—消化系统]