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机构地区:[1]重庆医科大学附属第二医院肝胆外科,重庆400010
出 处:《解放军医学杂志》2009年第6期729-732,共4页Medical Journal of Chinese People's Liberation Army
基 金:国家自然科学基金资助项目(30500473)
摘 要:目的观察肝组织清道夫受体A(SR-A)和脂多糖(LPS)受体CD14在内毒素介导的急性肝损伤中的表达及其意义。方法Wistar大鼠90只,随机均分为内毒素血症(LPS)组和生理盐水注射(NS)组,LPS组经尾静脉注射LPS5mg/kg,建立内毒素血症和急性肝损伤动物模型。NS组尾静脉注射0.2ml生理盐水作为对照。分别于注射后0、1.5、3、6、12h检测血浆LPS、TNF-α、IL-1、丙氨酸转氨酶(ALT)及总胆红素(TB)含量,肝组织中SR-A和CD14蛋白表达情况。光镜观察肝组织病理变化,电镜观察库普弗细胞(KCs)超微结构的变化,并测定KCs的吞噬功能。结果随时间延长,LPS组KCs从形态和功能上呈现激活改变(数量增多、体积增大、吞噬功能增强),血浆TNF-α、IL-1含量明显增加,肝细胞变性、坏死等病理改变以及肝功能损害进行性加重,同时肝组织中SR-A表达明显下降、CD14表达明显升高(P<0.01)。结论肝组织中进行性的SR-A表达下降和CD14表达增强可能是内毒素介导急性肝损伤的重要机制之一。Objective To investigated the expression of scavenger receptor A (SR-A) and lipopolysaccharide (LPS) receptor CD14 in endotoxin-induced acute liver injury. Methods Ninety Wistar rats were randomly divided into endotoxaemia group (LPS group) and normal saline group (NS group). The model of endotoxaemia and acute endotoxin-induced liver injury was established by injection of endotoxin (5mg/kg) via tail veins in LPS group, while the rats in NS group received injection of 0. 2ml normal saline as control. At 0, 1.5, 3, 6, 12h after injection, the levels of endotoxin, TNF-α, IL-1, alanine transarninase (ALT) and total bilirubin (TB) in plasma, SR-A and CD14 expressions in liver tissues were determined, pathological changes of liver tissues and ultrastructural changes of Kupffer cells (KCs) were observed by light and electron microscopy respectively, while the phagocytosis of KCs was determined too. Results Compared with NS group, KCs were activated on morphology and functions (proliferated diffusely, enlarged in size and increased in phagocytosis function), levels of TNF-α and IL-1 increased markedly, the pathological changes of cell degeneration and necrosis and the liver function were gradually aggravated, while SR A expression decreased and CD14 expression increased obviously (P〈0.01) in LPS group with the lapse of time. Conclusion The down-regulating of SR-A expression and up-regulating of CD14 expression progressively in liver tissues may play an important role in endotoxin-induced acute liver injury.
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