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IL-17A基因敲除减轻脂多糖诱导的脂肪肝小鼠肝脏炎症性损伤及其机制

发布时间:2018-03-02 12:42

  本文选题:白介素A 切入点:脂肪肝 出处:《第三军医大学学报》2017年16期  论文类型:期刊论文


【摘要】:目的在长程高脂膳食诱导的脂肪肝小鼠中,探讨白介素17A(interleukin 17A,IL-17A)基因缺陷对脂多糖(lipopolysaccharide,LPS)诱导的急性肝损伤的作用及其可能的机制。方法利用IL-17A基因敲除小鼠构建脂肪肝急性损伤模型,通过检测血浆中谷丙转氨酶(alanine transaminase,ALT)和谷草转氨酶(aspartate transaminase,AST)评估肝脏损伤情况,通过检测血浆中3种主要炎症因子TNF-α、IL-1β以及IL-6评估机体炎症水平,通过肝脏病理形态观测肝脏组织炎症细胞浸润和肝细胞损伤情况。通过对肝脏组织表达mRNA进行转录组学分析,寻找IL-17A基因敲除在高脂膳食(high fat diet,HF)+LPS诱导的肝损伤中的发挥作用的相关分子信号机制。结果在高脂膳食喂养辅之以一次性LPS刺激下,IL-17A基因敲除(gene knockout,KO)小鼠血浆中的ALT及AST水平显著降低(P0.05);KO小鼠血浆中炎症因子水平显著降低(P0.05),肝脏组织中浸润的炎症细胞显著减少(P0.05)。肝脏转录组学分析结果显示,刺激后,KO小鼠下调的938个基因主要富集于氧化应激(P0.01)、过氧化氢代谢途径(P0.01)以及谷胱甘肽代谢途径(P0.01)。Real-time PCR检测发现KO小鼠肝脏中与过氧化氢代谢相关的CAT、GPX1、IDH1、IDH2以及ME1基因的mRNA水平显著升高。同时,肝脏的氧化应激水平显著降低(P0.05)。TUNEL检测进一步检测结果显示,KO小鼠肝脏凋亡细胞数量显著减少(P0.01)。结论 IL-17A基因敲除可能通过促进过氧化氢代谢减轻LPS诱导的脂肪肝小鼠急性炎症性肝损伤。
[Abstract]:Objective to investigate the effect of interleukin 17Am interleukin 17A (IL-17A) gene deficiency on acute liver injury induced by lipopolysaccharide (LPS) and its possible mechanism in mice with fatty liver induced by long-term high fat diet. Methods Acute fatty liver injury model was established by using IL-17A gene knockout mice. The liver injury was assessed by detecting alanine transaminase (alt) and aspartate transaminase (AST) in plasma, and the level of inflammation was assessed by detecting three major inflammatory factors TNF- 伪 IL-1 尾 and IL-6. The infiltration of inflammatory cells and the damage of liver cells were observed by pathological morphology of liver. The expression of mRNA in liver tissue was analyzed by transcriptome. To search for the molecular signaling mechanism of IL-17A knockout in liver injury induced by high fat dietadine (HFH) LPS in high fat diet. Results in the plasma of mice fed with high fat diet supplemented with one-off LPS stimulation, IL-17A gene knockout Ko gene knockout Ko. The levels of ALT and AST were significantly decreased in P0.05KO mice. The levels of plasma inflammatory cytokines and infiltrating inflammatory cells in liver tissue were significantly decreased in P0.05KO mice. The results of transcriptome analysis of liver showed that the level of inflammatory cytokines in the plasma of P0.05KO mice was significantly lower than that of P0.05KO mice. The down-regulated 938 genes in KO mice were mainly enriched in oxidative stress P0.01a, hydrogen peroxide metabolism pathway P0.01and glutathione metabolism pathway P0.01. Real-time PCR analysis showed that CATGPX1IDH1IDH2 and ME1 genes were related to hydrogen peroxide metabolism in liver of KO mice. At the same time, the level of mRNA increased significantly. The level of oxidative stress in the liver was significantly reduced. Tunel assay showed that the number of apoptotic cells in liver of KO mice was significantly reduced. Conclusion IL-17A knockout may alleviate fatty liver induced by LPS by promoting hydrogen peroxide metabolism. Acute inflammatory liver injury in mice.
【作者单位】: 第三军医大学基础医学院生物化学与分子生物学教研室;第三军医大学西南医院病理研究所;第三军医大学大坪医院野战外科研究所肝胆外科;
【基金】:国家自然科学基金面上项目(81270482)~~
【分类号】:R575


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