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ESTABLISHMENT AND EVALUATION OF ANIMAL MODELS TO ELUCIDATE THE PATHOPHYSIOLOGY OF MULTIPLE ORGAN DYSFUNCTION SYNDROME

动物模型的建立和评估以阐明多器官功能障碍综合征的病理生理学

基本信息

批准号：
11671526
负责人：
KOIKE Kaoru
金额：
$ 2.24万
依托单位：
Tohoku University (2001)Nippon Medical School (1999-2000)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671526/
关键词：
intestine ischemia reperfusion injury phospholipase A2 rat mouse lung injury liver injury

项目摘要

[1] We have previously reported that intestinal ischemia-reperfusion (I/R) produced lung injury via a mechanism which involves phospholipase A2 (PLA2) activation. In this study we hypothesized that group IIA PLA2 is the responsible isozyme. Intestinal I/R provoked intestinal leak, liver injury, and lung leak, while tissue PLA2 activity was decreased in the intestine, unchanged in the liver, and increased in the lung. Serum PLA2 activities increased in the portal and systemic circulation during ischemia. Pretreatment with S-5920/LY315920Na eliminated PLA2 activities in all tissues and sera, and only abolished lung leak. Intestinal ischemia-reperfusion appears to produce lung injury via a mechanism which involves group IIA PLA2 activation. Intestinal I/R is likely to promote intestinal and hepatic injury independent of group IIA PLA2.[2] While various animal models have been used to elucidate what causes multiple organ failure, definite methods to estimate systemic organ damage, especial … More ly endothelial injury, have not well been established in mice. We attempted to establish simple methods that enable us to detect intestinal, pulmonary, and hepatic injury in a murine model of intestinal I/R. Adult female BALB/c mice underwent 45 minutes of superior mesenteric artery occlusion. Two and 6 hours after reperfusion, microvascular permeability and edema formation in the intestine, lung, and liver, were quantitated by Evans blue method (EB) and wet/dry ratio (W/D), respectively. Liver function was also measured by plasma alanine aminotransferase (ALT) and total bilirubin (T-Bil) concentrations. In BALB/c mice, intestinal injury was detected by EB and W/D, and increased pulmonary permeability was measured by EB. Liver injury was quantitated by EB, W/D, and T-Bil. In C57BL/6 mice, intestinal injury was estimated by EB and W/D, lung leak by EB, and liver injury by W/D, ALT, and T-Bil. While slight difference was observed between those two strains of mice, intestinal, pulmonary and hepatic injury could be successfully estimated by the combination of EB, W/D, ALT and T-Bil in a murine model of intestinal I/R. These methods may become useful in mice not only to delineate the mechanisms linking intestinal I/R and remote organ injury but also in other fields of shock research. Less

[1]我们以前曾报道过肠缺血再灌注（I/R）通过磷脂酶A2（PLA 2）激活机制引起肺损伤。在这项研究中，我们假设IIA组PLA 2是负责的同工酶。肠I/R引起肠漏、肝损伤和肺漏，而组织PLA 2活性在肠中降低，在肝中不变，在肺中增加。缺血时门脉和体循环中的血清PLA 2活性升高。S-5920/LY 315920 Na预处理可消除所有组织和血清中的PLA 2活性，仅消除肺渗漏。肠缺血-再灌注似乎通过涉及IIA族PLA 2活化的机制产生肺损伤。肠I/R可能独立于IIA组PLA 2促进肠和肝损伤。[2]虽然各种动物模型已被用来阐明是什么原因导致多器官衰竭，确定的方法来估计全身器官损害，特别是 ...更多信息即内皮损伤，在小鼠中还没有很好地建立。我们试图建立简单的方法，使我们能够检测肠I/R小鼠模型中的肠、肺和肝损伤。成年雌性BALB/c小鼠经历45分钟的上级肠系膜动脉闭塞。再灌注后2 h和6 h，分别用伊文思蓝法（EB）和湿/干比（W/D）定量肠、肺和肝微血管通透性和水肿形成。还通过血浆丙氨酸氨基转移酶（ALT）和总胆红素（T-Bil）浓度来测量肝功能。在BALB/c小鼠中，通过EB和W/D检测肠损伤，并通过EB测量肺通透性增加。用EB、W/D和T-Bil定量肝损伤。在C57 BL/6小鼠中，通过EB和W/D评估肠损伤，通过EB评估肺渗漏，通过W/D、ALT和T-Bil评估肝损伤。虽然这两个品系的小鼠之间观察到轻微的差异，但在肠I/R小鼠模型中，通过EB、W/D、ALT和T-Bil的组合可以成功地评估肠、肺和肝的损伤。这些方法可能成为有用的小鼠不仅描绘肠I/R和远程器官损伤的机制，而且在休克研究的其他领域。少