Zantl N, Uebe A, Neumann B, Wagner H, Siewert J R, Holzmann B, Heidecke C D, Pfeffer K
Institute of Medical Microbiology, Immunology and Hygiene and Department of Surgery, Klinikum rechts der Isar, Technical University of Munich, Germany.
Infect Immun. 1998 May;66(5):2300-9. doi: 10.1128/IAI.66.5.2300-2309.1998.
Despite considerable progress, peritonitis and sepsis remain life-threatening conditions. To improve the understanding of the pathophysiology encountered in sepsis, a new standardized and highly reproducible murine model of abdominal sepsis termed colon ascendens stent peritonitis (CASP) was developed. In CASP, a stent is inserted into the ascending colon, which generates a septic focus. CASP employing a stent of 14-gauge diameter (14G stent) results in a mortality of 100% within 18 to 48 h after surgery. By inserting stents of small diameters, mortality can be exactly controlled. Thus, CASP surgery with insertion of a 22G or 18G stent (22G or 18G CASP surgery) results in 38 or 68% mortality, respectively. 14G CASP surgery leads to a rapid invasion of bacteria into the peritoneum and the blood. As a consequence, endotoxemia occurs, inflammatory cells are recruited, and a systemic inflammatory response syndrome develops. Interestingly, the most pronounced upregulation of inflammatory cytokines (gamma interferon [IFN-gamma], tumor necrosis factor alpha [TNF-alpha] and interleukin-12) is observed in spleen and lungs. CASP surgery followed by stent removal at specific time intervals revealed that all animals survived if intervention was performed after 3 h, whereas removal of the septic focus after 9 h did not prevent death, suggesting induction of autonomous mechanisms of a lethal inflammatory response syndrome. 18G CASP surgery in IFN-gamma receptor-deficient (IFNgammaR-/-) mice revealed an essential role of IFN-gamma in survival of sepsis, whereas TNF receptor p55-deficient (TNFRp55-/-) mice did not show altered survival rates. In summary, this study describes a novel animal model that closely mimics human sepsis and appears to be highly suitable for the study of the pathophysiology of abdominal sepsis. Importantly, this model demonstrates a protective role of IFN-gamma in survival of bacterial sepsis.
尽管取得了显著进展，但腹膜炎和脓毒症仍然是危及生命的病症。为了增进对脓毒症病理生理学的理解，开发了一种新的标准化且高度可重复的腹部脓毒症小鼠模型，称为升结肠支架腹膜炎（CASP）。在CASP模型中，将一个支架插入升结肠，从而产生一个感染灶。采用14号直径支架（14G支架）的CASP模型在手术后18至48小时内死亡率为100%。通过插入小直径的支架，可以精确控制死亡率。因此，插入22G或18G支架的CASP手术（22G或18G CASP手术）死亡率分别为38%或68%。14G CASP手术会导致细菌迅速侵入腹膜和血液。结果，发生内毒素血症，炎症细胞被募集，进而发展为全身炎症反应综合征。有趣的是，在脾脏和肺中观察到炎症细胞因子（γ干扰素[IFN-γ]、肿瘤坏死因子α[TNF-α]和白细胞介素-12）最显著的上调。在特定时间间隔进行CASP手术后移除支架，结果显示如果在3小时后进行干预，所有动物都能存活，而在9小时后移除感染灶并不能防止死亡，这表明诱导了致命性炎症反应综合征的自主机制。在γ干扰素受体缺陷（IFNγR-/-）小鼠中进行18G CASP手术表明，γ干扰素在脓毒症存活中起重要作用，而肿瘤坏死因子受体p55缺陷（TNFRp55-/-）小鼠的存活率没有改变。总之，本研究描述了一种新的动物模型，该模型能紧密模拟人类脓毒症，似乎非常适合用于研究腹部脓毒症的病理生理学。重要的是，该模型证明了γ干扰素在细菌性脓毒症存活中的保护作用。
