脂多糖诱导脓毒症大鼠脑内氧化损伤及相关信号通路的研究  

Oxidative damage and related signal pathways caused by lipopolysaccharide induced sepsis in rat brain

作　　者：陈锋[1,2] 刘英富[2] 李光宗[2] 张益[2] 郁硕 樊毫军[2] 侯世科[1,2] 

机构地区：[1]天津医科大学研究生院,天津300070 [2]武警后勤学院附属医院救援医学研究所,天津300162

出　　处：《军事医学》2016年第9期703-706,共4页Military Medical Sciences

基　　金：天津市科技计划资助项目(14ZCDZSY00033);天津市应用基础与前沿技术研究计划资助项目(14JCQNJC12600);全军重点实验室开放基金资助项目(JY1402)

摘　　要：目的探讨脂多糖(lipopolysaccharide,LPS)诱导的脓毒症造成大鼠脑内氧化损伤的作用及JNK、Nrf2相关信号的变化。方法将大鼠随机分为对照组、低剂量模型组(LPS 5 mg/kg)和高剂量模型组(LPS 10 mg/kg)。模型组造模24 h后,活杀大鼠,将脑组织完全取出后,剪碎并研磨成脑匀浆,检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)、过氧化氢(H2O2)、琥珀酸脱氢酶(SDH)的变化。利用qRT-PCR、Western印迹检测JNK与Nrf2蛋白在脑组织亚细胞中的表达水平。结果与对照组比较,在LPS诱导脓毒症大鼠模型中,模型组大鼠脑组织中,MDA、H2O2、SDH含量增加,SOD、GSH-Px、T-AOC含量减少,JNK mRNA水平与总蛋白水平未受明显影响(P>0.05),但磷酸化水平(p-JNK)显著升高(P<0.01);Nrf2 mRNA水平与总蛋白水平显著上调(P<0.01),且磷酸化水平(p-Nrf2)也显著升高(P<0.01),差异具有统计学意义。结论成功构建LPS诱导脓毒血症后大鼠脑内氧化损伤的病理模型,并发现在这一病理过程中p-JNK、总Nrf2以及p-Nrf2表达显著上调,提示JNK、Nrf2相关通路在LPS诱导脓毒症脑损伤中可能参与重要的介导作用。Objective To investigate the mechanism of oxidative damage caused by lipopolysaccharide （LPS）induced sepsis in rat brain.Methods The rats were randomly divided into control group and model group （low LPS group and high LPS group）.Twenty-four hours after the modeling,the rats were sacrificed before their brain tissue was taken out and prepared for the test.The changes in malondialdehyde （MDA）,superoxide dismutase （SOD）,glutathione peroxidase （GSH-Px）,total antioxidant capacity （T-AOC）,hydrogen peroxide （H2 O2 ）and succinate dehydrogenase （SDH）were detected.The expression level of JNK and Nrf2 protein in brain tissue was detected by qRT-PCR and Western blotting. Results Compared with the control group,the MDA,SOD,GSH-px,T-AOC,H2O2 and SDH level increased significantly in the model group,and the difference in expressions of JNK and Nrf2 was statistically significant （P 〈0.05）. Conclusion The LPS induced septic oxidative brain damage model in rats is successfully established,and the process may be regulated through the Nrf2 and JNK signal pathways.

关 键 词：脂多糖类 脓毒症 脑损伤 丙二醛 超氧化物歧化酶 过氧化氢 琥珀酸脱氢酶 

分 类 号：R459.7[医药卫生—急诊医学]