枯否细胞封闭对内毒素介导肝脏MAPK和STAT信号转导的影响

发布时间：2018-06-16 00:10

  本文选题：枯否细胞 + 内毒素　； 参考：《山西医科大学》2006年硕士论文

【摘要】： 目的:内毒素激活肝脏枯否细胞(kupffer cells, KCs)丝裂原活化蛋白激酶(mitogen-activated protein kinases, MAPK)信号转导通路,Janus激酶(janus protein tyrosine kinase, JAK)/信号转导子与转录激活子(signal transducer and activator of transcription, STATs)即JAK/STAT信号转导通路,使其大量分泌释放TNF-α、ROS等活性物质,导致肝脏发生氧化应激,引起肝损伤。三氯化钆(gadolinium chloride, GdCl_3)可抑制KCs活化,减轻内毒素所致肝损伤,但封闭KCs是否是可以通过调节MAPK、JAK/STAT信号转导通路来实现肝脏保护作用尚未阐明。为此本实验利用小鼠内毒素血症模型,探讨KCs封闭对内毒素介导肝脏上述信号转导的影响。 方法:Ⅰ雄性昆明种小鼠连续二天尾静脉分别注射GdCl_3(10mg/kg)或等量的生理盐水,第三天腹腔注射半乳糖胺/脂多糖(Galn/LPS)(13mg/3ug/只)或生理盐水,分别于Galn/LPS或生理盐水注射后0.5h、1h、1.5h、6h内眦静脉取血,测血浆ALT活性,取肝脏测其GSH、MDA、TNF-α含量。Ⅱ雄性昆明种小鼠连续二天尾静脉分别注射GdCl_3(10mg/kg)或等量的生理盐水,第三天腹腔注射LPS(5mg/kg)或等量的生理盐水,分别于0.5h、2h、6h后取出肝脏,检测肝脏MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白表达及磷酸化水平。 结果:经GdCl_3预处理动物血浆ALT活性和肝脏MDA含量明显下降,而GSH含量则升高。LPS可促进肝脏MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表达;GdCl_3预处理能不同程度地抑制LPS诱导的肝脏MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表达。 结论:GdCl_3可通过封闭KCs减轻LPS诱导肝内TNF-α、ROS等活性物质的释放,增强肝脏抗氧化应激能力,从而保护肝脏。GdCl_3封闭KCs可通过调节肝脏MAPK与JAK/STAT信号转导通路,实现肝脏保护作用。
[Abstract]:Aim: endotoxin activated Kupffer cells (KCs) mitogen-activated protein kinases (MAPKs) signal transduction pathway, Janus kinase protein tyrosine kinase, signal transducers and activator signal transducer and activator of transcription, STATs-JAK / STAT signal transduction pathway. It can release TNF- 伪 Ros and other active substances in a large amount, resulting in oxidative stress in liver and liver injury. Gadolinium chloride (GdCl3) can inhibit the activation of KCs and reduce the hepatic injury induced by endotoxin. However, whether blocking KCs can protect the liver by regulating MAPK- JAK / stat signal transduction pathway has not been clarified. In order to investigate the effect of KCs blocking on endotoxin-mediated hepatic signal transduction in mice, the model of endotoxemia was used in this study. Methods: male Kunming mice were injected with GdCl _ (3 + 10 mg 路kg ~ (-1) 路kg ~ (-1) or the same amount of normal saline in tail vein for two consecutive days. On the third day, intraperitoneal injection of galactosamine / lipopolysaccharide Galn / LPSN (13 mg / 3 ugg / mouse) or normal saline was used to collect blood from canthus vein within 0.5 h after LPS injection or normal saline injection. Plasma alt activity was measured and the content of GSH MDA-TNF- 伪 was measured in the liver. 鈪，

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