急性肝衰竭小鼠血清TNFα 与血脑屏障通透性的改变

 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。

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

Objective To investigate the changes of serum tumor necrosis factor（TNF）αlevel and the blood-brain barrier（BBB）perme-
ability 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 TNFαwere determined. The liver tissues were fixed for histopathologic analysis. The perme-
ability 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 TNFαwas 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 TNFαlevel was obviously in-
creased，which was consistent with the increased concentration of EB in brain tissue. TNFαmight be an important cytokine that increased the
permeability of BBB in APAP-induced ALF.