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

发布时间：2018-06-27 07:47

本文选题：脂多糖类 + 脓毒症　；参考：《军事医学》2016年09期

【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(P0.05),但磷酸化水平(p-JNK)显著升高(P0.01);Nrf2 mRNA水平与总蛋白水平显著上调(P0.01),且磷酸化水平(p-Nrf2)也显著升高(P0.01),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。
[Abstract]:Objective to investigate the effects of lipopolysaccharide (LPS) -induced sepsis on oxidative damage in rat brain and the changes of JNK-Nrf2 related signals. Methods Rats were randomly divided into control group, low dose model group (LP5 mg/kg) and high dose model group (LPS-10 mg/kg). In the model group, after 24 hours of modeling, the rats were killed alive, the brain tissue was completely removed, and the brain homogenate was cut and ground into a brain homogenate. Malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), hydrogen peroxide (H2O2) and succinate dehydrogenase (SDH) were measured. The expression of JNK and Nrf2 proteins in brain subcells was detected by qRT-PCR- Western blot. Results compared with the control group, in LPS induced sepsis rat model, In the model group, the content of SDH in the brain tissue of MDA-H _ 2O _ 2 increased and the content of GSH-PxX T-AOC decreased significantly (P0.05), but the level of phosphorylation (p-JNK) increased significantly (P0.01), and the level of phosphorylation (p-Nrf2) also increased significantly (P0.01), and the level of phosphorylation (p-Nrf2) was also significantly increased (P0.01), while the level of phosphorylation (p-Nrf2) was also significantly increased (P0.01), while the level of phosphorylation (p-Nrf2) was also significantly increased (P0.01). The difference was statistically significant (P0.01). Conclusion the pathological model of oxidative injury induced by LPS in rats with sepsis was successfully constructed, and it was found that the expression of p-JNK2, total Nrf2 and p-Nrf2 were significantly up-regulated during the pathological process. These results suggest that JNKN Nrf2 pathway may play an important role in LPS induced septic brain injury.
【作者单位】：天津医科大学研究生院;武警后勤学院附属医院救援医学研究所;
【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)
【分类号】：R459.7

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