發(fā)布時(shí)間：2018-06-16 00:10

  本文選題：枯否細(xì)胞 + 內(nèi)毒素��； 參考：《山西醫(yī)科大學(xué)》2006年碩士論文

【摘要】： 目的:內(nèi)毒素激活肝臟枯否細(xì)胞(kupffer cells, KCs)絲裂原活化蛋白激酶(mitogen-activated protein kinases, MAPK)信號(hào)轉(zhuǎn)導(dǎo)通路,Janus激酶(janus protein tyrosine kinase, JAK)/信號(hào)轉(zhuǎn)導(dǎo)子與轉(zhuǎn)錄激活子(signal transducer and activator of transcription, STATs)即JAK/STAT信號(hào)轉(zhuǎn)導(dǎo)通路,使其大量分泌釋放TNF-α、ROS等活性物質(zhì),導(dǎo)致肝臟發(fā)生氧化應(yīng)激,引起肝損傷。三氯化釓(gadolinium chloride, GdCl_3)可抑制KCs活化,減輕內(nèi)毒素所致肝損傷,但封閉KCs是否是可以通過(guò)調(diào)節(jié)MAPK、JAK/STAT信號(hào)轉(zhuǎn)導(dǎo)通路來(lái)實(shí)現(xiàn)肝臟保護(hù)作用尚未闡明。為此本實(shí)驗(yàn)利用小鼠內(nèi)毒素血癥模型,探討KCs封閉對(duì)內(nèi)毒素介導(dǎo)肝臟上述信號(hào)轉(zhuǎn)導(dǎo)的影響。 方法:Ⅰ雄性昆明種小鼠連續(xù)二天尾靜脈分別注射GdCl_3(10mg/kg)或等量的生理鹽水,第三天腹腔注射半乳糖胺/脂多糖(Galn/LPS)(13mg/3ug/只)或生理鹽水,分別于Galn/LPS或生理鹽水注射后0.5h、1h、1.5h、6h內(nèi)眥靜脈取血,測(cè)血漿ALT活性,取肝臟測(cè)其GSH、MDA、TNF-α含量。Ⅱ雄性昆明種小鼠連續(xù)二天尾靜脈分別注射GdCl_3(10mg/kg)或等量的生理鹽水,第三天腹腔注射LPS(5mg/kg)或等量的生理鹽水,分別于0.5h、2h、6h后取出肝臟,檢測(cè)肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白表達(dá)及磷酸化水平。 結(jié)果:經(jīng)GdCl_3預(yù)處理動(dòng)物血漿ALT活性和肝臟MDA含量明顯下降,而GSH含量則升高。LPS可促進(jìn)肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表達(dá);GdCl_3預(yù)處理能不同程度地抑制LPS誘導(dǎo)的肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表達(dá)。 結(jié)論:GdCl_3可通過(guò)封閉KCs減輕LPS誘導(dǎo)肝內(nèi)TNF-α、ROS等活性物質(zhì)的釋放,增強(qiáng)肝臟抗氧化應(yīng)激能力,從而保護(hù)肝臟。GdCl_3封閉KCs可通過(guò)調(diào)節(jié)肝臟MAPK與JAK/STAT信號(hào)轉(zhuǎn)導(dǎo)通路,實(shí)現(xiàn)肝臟保護(hù)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- 偽 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- 偽 was measured in the liver. 鈪，

本文編號(hào)：2024280