Luo Shuhua, Tang Menglin, Du Lei, Gong Lina, Xu Jin, Chen Youwen, Wang Yabo, Lin Ke, An Qi
Department of Cardiovascular Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Intensive Care Unit, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Mediators Inflamm. 2015;2015:412319. doi: 10.1155/2015/412319. Epub 2015 Jan 29.
Extracorporeal circulation (ECC) is necessary for conventional cardiac surgery and life support, but it often triggers systemic inflammation that can significantly damage tissue. Studies of ECC have been limited to large animals because of the complexity of the surgical procedures involved, which has hampered detailed understanding of ECC-induced injury. Here we describe a minimally invasive mouse model of ECC that may allow more extensive mechanistic studies. The right carotid artery and external jugular vein of anesthetized adult male C57BL/6 mice were cannulated to allow blood flow through a 1/32-inch external tube. All animals (n = 20) survived 30 min ECC and subsequent 60 min observation. Blood analysis after ECC showed significant increases in levels of tumor necrosis factor α, interleukin-6, and neutrophil elastase in plasma, lung, and renal tissues, as well as increases in plasma creatinine and cystatin C and decreases in the oxygenation index. Histopathology showed that ECC induced the expected lung inflammation, which included alveolar congestion, hemorrhage, neutrophil infiltration, and alveolar wall thickening; in renal tissue, ECC induced intracytoplasmic vacuolization, acute tubular necrosis, and epithelial swelling. Our results suggest that this novel, minimally invasive mouse model can recapitulate many of the clinical features of ECC-induced systemic inflammatory response and organ injury.
体外循环(ECC)对于传统心脏手术和生命支持是必要的,但它常常引发可显著损害组织的全身炎症。由于所涉及手术程序的复杂性,ECC的研究一直局限于大型动物,这阻碍了对ECC诱导损伤的详细了解。在此,我们描述了一种ECC的微创小鼠模型,它可能允许进行更广泛的机制研究。将麻醉的成年雄性C57BL/6小鼠的右颈动脉和颈外静脉插管,以使血液流经一根1/32英寸的外置管。所有动物(n = 20)在进行30分钟的ECC及随后60分钟的观察后均存活。ECC后的血液分析显示,血浆、肺和肾组织中的肿瘤坏死因子α、白细胞介素-6和中性粒细胞弹性蛋白酶水平显著升高,同时血浆肌酐和胱抑素C增加,氧合指数降低。组织病理学显示,ECC诱导了预期的肺部炎症,包括肺泡充血、出血、中性粒细胞浸润和肺泡壁增厚;在肾组织中,ECC诱导了胞浆内空泡化、急性肾小管坏死和上皮肿胀。我们的结果表明,这种新型的微创小鼠模型能够概括ECC诱导的全身炎症反应和器官损伤的许多临床特征。