發(fā)布時間：2018-06-16 00:10

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

【摘要】： 目的:內(nèi)毒素激活肝臟枯否細胞(kupffer cells, KCs)絲裂原活化蛋白激酶(mitogen-activated protein kinases, MAPK)信號轉導通路,Janus激酶(janus protein tyrosine kinase, JAK)/信號轉導子與轉錄激活子(signal transducer and activator of transcription, STATs)即JAK/STAT信號轉導通路,使其大量分泌釋放TNF-α、ROS等活性物質(zhì),導致肝臟發(fā)生氧化應激,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是否是可以通過調(diào)節(jié)MAPK、JAK/STAT信號轉導通路來實現(xiàn)肝臟保護作用尚未闡明。為此本實驗利用小鼠內(nèi)毒素血癥模型,探討KCs封閉對內(nèi)毒素介導肝臟上述信號轉導的影響。 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,測血漿ALT活性,取肝臟測其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,檢測肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白表達及磷酸化水平。 結果:經(jīng)GdCl_3預處理動物血漿ALT活性和肝臟MDA含量明顯下降,而GSH含量則升高。LPS可促進肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表達;GdCl_3預處理能不同程度地抑制LPS誘導的肝臟MEK1/2、ERK1/2、p38MAPK、STAT1、STAT3蛋白磷酸化表達。 結論:GdCl_3可通過封閉KCs減輕LPS誘導肝內(nèi)TNF-α、ROS等活性物質(zhì)的釋放,增強肝臟抗氧化應激能力,從而保護肝臟。GdCl_3封閉KCs可通過調(diào)節(jié)肝臟MAPK與JAK/STAT信號轉導通路,實現(xiàn)肝臟保護作用。
[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：2024280