發(fā)布時(shí)間：2018-03-02 12:42

  本文選題：白介素A　切入點(diǎn)：脂肪肝　出處：《第三軍醫(yī)大學(xué)學(xué)報(bào)》2017年16期 　論文類型：期刊論文

【摘要】：目的在長程高脂膳食誘導(dǎo)的脂肪肝小鼠中,探討白介素17A(interleukin 17A,IL-17A)基因缺陷對(duì)脂多糖(lipopolysaccharide,LPS)誘導(dǎo)的急性肝損傷的作用及其可能的機(jī)制。方法利用IL-17A基因敲除小鼠構(gòu)建脂肪肝急性損傷模型,通過檢測血漿中谷丙轉(zhuǎn)氨酶(alanine transaminase,ALT)和谷草轉(zhuǎn)氨酶(aspartate transaminase,AST)評(píng)估肝臟損傷情況,通過檢測血漿中3種主要炎癥因子TNF-α、IL-1β以及IL-6評(píng)估機(jī)體炎癥水平,通過肝臟病理形態(tài)觀測肝臟組織炎癥細(xì)胞浸潤和肝細(xì)胞損傷情況。通過對(duì)肝臟組織表達(dá)mRNA進(jìn)行轉(zhuǎn)錄組學(xué)分析,尋找IL-17A基因敲除在高脂膳食(high fat diet,HF)+LPS誘導(dǎo)的肝損傷中的發(fā)揮作用的相關(guān)分子信號(hào)機(jī)制。結(jié)果在高脂膳食喂養(yǎng)輔之以一次性LPS刺激下,IL-17A基因敲除(gene knockout,KO)小鼠血漿中的ALT及AST水平顯著降低(P0.05);KO小鼠血漿中炎癥因子水平顯著降低(P0.05),肝臟組織中浸潤的炎癥細(xì)胞顯著減少(P0.05)。肝臟轉(zhuǎn)錄組學(xué)分析結(jié)果顯示,刺激后,KO小鼠下調(diào)的938個(gè)基因主要富集于氧化應(yīng)激(P0.01)、過氧化氫代謝途徑(P0.01)以及谷胱甘肽代謝途徑(P0.01)。Real-time PCR檢測發(fā)現(xiàn)KO小鼠肝臟中與過氧化氫代謝相關(guān)的CAT、GPX1、IDH1、IDH2以及ME1基因的mRNA水平顯著升高。同時(shí),肝臟的氧化應(yīng)激水平顯著降低(P0.05)。TUNEL檢測進(jìn)一步檢測結(jié)果顯示,KO小鼠肝臟凋亡細(xì)胞數(shù)量顯著減少(P0.01)。結(jié)論 IL-17A基因敲除可能通過促進(jìn)過氧化氫代謝減輕LPS誘導(dǎo)的脂肪肝小鼠急性炎癥性肝損傷。
[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- 偽 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.
【作者單位】： 第三軍醫(yī)大學(xué)基礎(chǔ)醫(yī)學(xué)院生物化學(xué)與分子生物學(xué)教研室;第三軍醫(yī)大學(xué)西南醫(yī)院病理研究所;第三軍醫(yī)大學(xué)大坪醫(yī)院野戰(zhàn)外科研究所肝膽外科;
【基金】：國家自然科學(xué)基金面上項(xiàng)目(81270482)~~
【分類號(hào)】：R575
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本文編號(hào)：1556568