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Proteolytic activity and fatal gram-negative sepsis in burned mice: effect of exogenous proteinase inhibition.

机译:烧伤小鼠的蛋白水解活性和致命的革兰氏阴性败血症:外源蛋白酶抑制作用。

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Circulating proteolytic activity (PA) increases following burn or surgical trauma. Challenging traumatized mice with the yeast Candida albicans further increases PA. Once a PA threshold has been passed, mortality increases as PA increases. The purposes of this study were to determine (i) if gram-negative bacterial challenge affects circulating PA and mortality as Candida challenge does and (ii) if proteinase inhibitor treatment with aprotinin, antithrombin III, and alpha 1-proteinase inhibitor decreases circulating PA and increases the survival of burned mice infected with a bacterium. For all bacteria tested (Proteus mirabilis, Pseudomonas aeruginosa, and Klebsiella pneumoniae), burn plus challenge significantly elevated PA and mortality above levels in mice that were only burned or only challenged. Quantitative culture counts indicated that the mice died of sepsis. Proteinase inhibitor treatment of mice burned and challenged with K. pneumoniae significantly decreased circulating PA, decreased the hepatic microbial load, and increased survival. Hence, in traumatized mice challenged with either C. albicans or gram-negative bacteria, a relationship exists between proteolytic load and subsequent septic death. Parallels between these animal studies and human studies are discussed.
机译:烧伤或外科手术创伤后,循环蛋白水解活性(PA)增加。用酵母白色念珠菌攻击受创伤的小鼠可进一步提高PA。一旦超过PA阈值,死亡率就会随着PA的增加而增加。这项研究的目的是确定(i)革兰氏阴性细菌攻击是否像念珠菌攻击一样影响循环PA和死亡率,以及(ii)蛋白酶抑制剂,抑肽酶,抗凝血酶III和α1-蛋白酶抑制剂治疗是否能降低循环PA和增加了被细菌感染的烧伤小鼠的存活率。对于所有测试的细菌(奇异变形杆菌,铜绿假单胞菌和肺炎克雷伯菌),烧伤加激发显着提高了PA和死亡率,使其高于仅被烧伤或仅激发的小鼠。定量培养计数表明小鼠死于败血症。蛋白酶抑制剂治疗烧伤肺炎克雷伯氏菌并对其攻击的小鼠可显着降低循环PA,降低肝微生物负荷并提高生存率。因此,在受白色念珠菌或革兰氏阴性细菌攻击的受创伤小鼠中,蛋白水解负荷与随后的败血性死亡之间存在关系。讨论了这些动物研究与人类研究之间的平行之处。

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