摘要
目的探索LPS/D-gal诱导的急性肝炎中mTOR信号的变化。方法LPS/D-gal通过腹腔注射ICR雌性小鼠诱导急性肝炎模型。观察记录24h内的存活率或在注射后6h收集血清和肝脏组织样本,进行相关的分析。结果LPS/D-gal注射24h内引起小鼠急性死亡。注射后6h,引起血清中转氨酶水平明显升高。肝脏组织炎性因子Tnfa和Il6表达水平上调。HE染色显示明显的炎症细胞浸润,研究结果表明LPS/D-gal可诱导ICR小鼠成为急性肝炎动物模型。此外,肝脏组织免疫印迹分析发现,mTOR和NF-κB信号通路被激活,凋亡相关蛋白Caspase-3的活性增加,凋亡特征性的DNA片段化也显著增强。然而mTOR信号的抑制剂雷帕霉素并不能控制LPS/D-gal引起的肝脏凋亡和提高存活率。结论mTOR信号在LPS/D-gal诱导的急性肝炎的致病机制中可能发挥多重作用。
Objective To explore the changes of mTOR signaling in LPS/D-gal-induced acute hepatitis in mice.Methods Twenty-six healthy adult female ICR mice were divided into two groups: the control group and experimental group,13 mice in each group. LPS / D-gal was used to induce acute hepatitis in the mice. The survival of mice was monitored within 24 hours after LPS / D-gal challenge. At 6 hours after challenge,samples of serum and liver tissue were collected for further analysis. Results Injection of LPS / D-gal resulted in acute death of the mice within 24 hours. At 6 hours post LPS / D-gal injection,the blood levels of ALT and AST were significantly increased. The mRNA expression of inflammatory cytokines Tnfa and Il6 was up-regulated in LPS / D-gal-induced hapatitis,in which DNA fragmentation and activation of caspase-3 were subsequently observed. Immunoblot analysis showed that both mTOR pathway and NF-κB pathway were activated. Unexpectedly,inhibition of mTOR signaling could neither decrease the apoptosis in the liver nor increase the survival of mice. Conclusions The results of the present study indicate that mTOR signaling may play pleiotropic roles in the pathogenesis of LPS / D-gal-induced hepatitis.
出处
《中国实验动物学报》
CAS
CSCD
北大核心
2015年第3期306-311,共6页
Acta Laboratorium Animalis Scientia Sinica
基金
医学生物学研究所人才引进项目(IMB201)
云南省应用基础研究计划项目(2013FZ143)
