肠淋巴液致休克大鼠多器官损伤的作用及机制研究

发布时间：2018-04-30 17:04

本文选题：休克 + 失血性　；参考：《浙江大学》2006年博士论文

【摘要】：失血性休克(hemorrhagic shock)是临床常见急症,在失血性休克的发展过程中,会引起肠道屏障功能障碍和肠内细菌/内毒素移位(bacteria/endotoxin translocation,BET),导致肠源性感染,进而引起肺、肝、心、肾等多个器官的功能改变,诱发多器官功能障碍综合征(multiple organ dysfunction syndrome,MODS),严重威胁着人类生命,常常导致病人死亡。失血性休克致器官损伤的发生机制可能与休克引起失控的全身炎症反应综合征(systemic inflammatory response syndrome,SIRS)以及肠源性内毒素血症等环节有关。淋巴学是循环系统研究的薄弱领域,长期以来,一直认为淋巴途径是血液循环回流的辅助部分。作者多年的研究工作发现,淋巴微循环与休克的发生、发展及转归关系密切,结扎肠系膜淋巴管阻断肠淋巴液回流,可减轻二次打击大鼠的器官功能障碍,降低炎症反应:同时,肠系膜淋巴液可活化在体和离体的中性粒细胞,促进急性肺损伤(acute lung injury,ALI)的发生。因此,淋巴循环在休克以及休克致器官损伤中的作用开始受到关注。目的本研究通过整体动物实验,观察肠系膜淋巴管结扎阻断淋巴回流对失血性休克大鼠多器官的损伤作用,从器官形态、功能及自由基(FR)、一氧化氮(NO)、肿瘤坏死因子(TNFα)、白介素-6(IL-6)的变化,探讨其发病学机制;同时建立大鼠肺微血管内皮细胞(pulmonary micro-vascular endothelial cells,PMVEC)的原代培养技术,在离体条件下研究休克淋巴液对PMVEC的损伤作用,观察休克淋巴液对PMVEC的形态、代谢活力、增殖与凋亡、凋亡相关基因及炎症介质基因表达的影响,阐明休克淋巴液对多器官损伤的细胞分子机制,进一步揭示肠淋巴液回流在休克发病学中的作用及意义。方法 1)大鼠重症失血性休克模型的复制大鼠肌注2%的戊巴比妥钠(50mg/kg)全身麻醉,无菌手术,行右侧颈总动脉和左侧颈静脉插管,舌静脉注射0.5%肝素(1ml/kg),全身抗凝。休克组及结扎组自颈总动脉缓慢放血(失血量以全血量的1/5计,全血量以体重1/13计),3min完成,以无菌林格式液瓶作
[Abstract]:Hemorrhagic shock is a common clinical emergency. During the development of hemorrhagic shock, it can cause intestinal barrier dysfunction and intestinal bacterial / endotoxin translocation, resulting in enterogenous infection, and then lung, liver and heart. Multiple organ dysfunction syndrome (MODS) is a serious threat to human life and often leads to death in patients with multiple organ dysfunction syndrome. The mechanism of organ injury caused by hemorrhagic shock may be related to systemic inflammatory response syndrome (SIRs) and intestinal endotoxemia. Lymphatics is a weak area of circulatory system research. For a long time, lymphatic pathway has been regarded as an auxiliary part of circulatory reflux. The authors have found that lymphatic microcirculation is closely related to the occurrence, development and outcome of shock. Ligation of mesenteric lymphatic vessels to block intestinal lymphatic fluid reflux can alleviate organ dysfunction in rats with secondary shock. Decrease of inflammatory response: mesenteric lymphatic fluid can activate neutrophils in vivo and in vitro and promote the development of acute lung injuryAli. Therefore, the role of lymphatic circulation in shock and shock-induced organ injury began to receive attention. Purpose The purpose of this study was to observe the effects of mesenteric lymphatic ligation on the injury of multiple organs in hemorrhagic shock rats by ligation of mesenteric lymphatic vessels. The function and the changes of free radical, nitric oxide, tumor necrosis factor TNF- 伪 and interleukin-6 were studied, and the primary culture technique of rat pulmonary microvascular endothelial cells (micro-vascular endothelial cells PMVECs) was established. The effects of lymphatic shock on PMVEC were studied in vitro. The effects of lymphatic shock on the morphology, metabolic activity, proliferation and apoptosis, expression of apoptosis-related genes and inflammatory mediators of PMVEC were observed. To elucidate the cellular and molecular mechanism of lymphatic shock on multiple organ injury and to further reveal the role and significance of intestinal lymphatic fluid reflux in the pathogenesis of shock. Method 1) replication of severe hemorrhagic shock in rats Rats were given intramuscular injection of 2% pentobarbital sodium (50 mg / kg) for general anesthesia, sterile operation, right common carotid artery and left jugular vein intubation, tongue vein injection of 0.5% heparin 1 ml / kg, systemic anticoagulation. Shock group and ligation group were slowly bleeding from the common carotid artery (the blood loss was 1 / 5 of the total blood volume, the whole blood volume was completed by weight 1 / 13 / min / 3 min, and the blood loss was completed in aseptic liquid bottle in the form of aseptic forest.
【学位授予单位】：浙江大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R363

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