研究背景和目的:肝移植術(shù)和肝切除術(shù)是治療良性和早期惡性肝臟疾病的有效手段,但是,肝移植術(shù)和行肝門(mén)阻斷的肝切除術(shù)在術(shù)后將不可避免的誘發(fā)肝臟缺血再灌注損傷,影響患者術(shù)后肝臟功能的恢復(fù),甚至?xí)T發(fā)患者圍手術(shù)期肝功能異常或急性衰竭。因此,研究肝臟缺血再灌注損傷的發(fā)生機(jī)制及尋找潛在的干預(yù)靶點(diǎn)具有實(shí)際臨床意義。前折疊素樣蛋白（Unconventional prefoldin RPB5 interactor,URI）,也被稱(chēng)為RNA聚合酶II第五亞基調(diào)節(jié)蛋白（RNA polymerase II subunit5-mediating protein,RMP）已被證實(shí)在糖代謝、調(diào)節(jié)基因轉(zhuǎn)錄,細(xì)胞凋亡,促進(jìn)腫瘤轉(zhuǎn)移等過(guò)程中發(fā)揮調(diào)節(jié)功能。近來(lái)又有研究發(fā)現(xiàn),URI可以影響核轉(zhuǎn)錄因子-κB（Nuclear factor-kappa B,NF-κB）信號(hào)通路的激活從而調(diào)節(jié)Il-6的轉(zhuǎn)錄促進(jìn)肝癌的轉(zhuǎn)移。NF-κB信號(hào)通路主要由單核巨噬細(xì)胞介導(dǎo),并是固有免疫反應(yīng)激活過(guò)程中的重要信號(hào)通路�；诖�,我們前期研究了URI在巨噬細(xì)胞系中對(duì)于NF-κB和絲裂原活化蛋白激酶（Mitogen-activated protein k... 

【文章來(lái)源】：中國(guó)人民解放軍海軍軍醫(yī)大學(xué)上海市 211工程院校

【文章頁(yè)數(shù)】：109 頁(yè)

【學(xué)位級(jí)別】：博士

【部分圖文】：

髓敲URI鼠的構(gòu)建及敲除效果鑒定

而且效果穩(wěn)定（結(jié)果來(lái)自 6 對(duì)同窩配對(duì)成年小鼠）。Fig 2的肝臟 Kupffer 細(xì)胞 URI 敲除水平相對(duì)于野生型小鼠在 1/2 左右，且異。為了驗(yàn)證此模型 URI 的敲除僅限于髓系來(lái)源細(xì)胞，我們獲取 WT臟組織，并經(jīng)過(guò) RT-PCR 后，比較 WT 組與 KO 組，肝組織 RMP 表并無(wú)明顯差異，如 Fig 2f 所示。

壞死 3 個(gè)參考項(xiàng)，依據(jù)損傷情況，每一項(xiàng)評(píng)分從 0-3 分，最后 3 項(xiàng)）為肝損傷的 Suzuki 評(píng)分，經(jīng)定量分析及統(tǒng)計(jì)學(xué)分析后，兩組得分用現(xiàn)KO組得分為5.50±1.05，WT組得分為3.83±0.75，有統(tǒng)計(jì)學(xué)差異，P=0量評(píng)分比較如 Fig 3b 所示。Sham 組小鼠得分均為 0 分。Fig 3c 為構(gòu)建管夾位置，可見(jiàn)夾閉后肝組織顏色發(fā)白，取下的肝標(biāo)本邊緣可見(jiàn)壞死

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期刊論文
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