Stack A M, Saladino R A, Siber G R, Thompson C, Marra M N, Novitsky T J, Fleisher G R
Division of Emergency Medicine, Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Crit Care Med. 1997 Jan;25(1):101-5. doi: 10.1097/00003246-199701000-00020.
To compare a recombinant bactericidal/permeability-increasing protein variant and a recombinant endotoxin-neutralizing protein.
Randomized, blinded, controlled study, using a rat model of sepsis.
Animal research facility.
Male Wistar rats.
An inoculum of 1.5 x 10(7) to 1.8 x 10(8) Escherichia coli O18ac K1, implanted in the peritoneum, produced bacteremia in 95% of animals after 1 hr. One hour after E. coli challenge, animals received recombinant bactericidal/permeability-increasing protein variant, recombinant endotoxin-neutralizing protein, or saline intravenously, followed by ceftriaxone and gentamicin intramuscularly.
Twenty-four (85.7%) of 28 animals receiving recombinant endotoxin-neutralizing protein (p < .001 vs. control) survived 7 days compared with nine (33.3%) of 27 recombinant bactericidal/permeability-increasing protein variant-treated (p < .001 vs. control) and two (6.5%) of 31 control animals.
Both recombinant endotoxin-neutralizing protein and recombinant bactericidal/permeability-increasing protein variant improved survival. Recombinant endotoxin-neutralizing protein was superior to recombinant bactericidal/permeability-increasing protein variant in its protective effect at the doses tested. Our results suggest that both proteins may be useful in the treatment of human Gram-negative sepsis.
比较一种重组杀菌/通透性增加蛋白变体和一种重组内毒素中和蛋白。
采用败血症大鼠模型进行随机、盲法、对照研究。
动物研究设施。
雄性Wistar大鼠。
将1.5×10⁷至1.8×10⁸的大肠杆菌O18ac K1接种于腹腔，1小时后95%的动物出现菌血症。大肠杆菌攻击1小时后，动物静脉注射重组杀菌/通透性增加蛋白变体、重组内毒素中和蛋白或生理盐水，随后肌肉注射头孢曲松和庆大霉素。
28只接受重组内毒素中和蛋白治疗的动物中有24只（85.7%）存活7天（与对照组相比，p<.001），而27只接受重组杀菌/通透性增加蛋白变体治疗的动物中有9只（33.3%）存活（与对照组相比，p<.001），31只对照动物中有2只（6.5%）存活。
重组内毒素中和蛋白和重组杀菌/通透性增加蛋白变体均能提高生存率。在所测试的剂量下，重组内毒素中和蛋白在保护作用方面优于重组杀菌/通透性增加蛋白变体。我们的结果表明，这两种蛋白可能对治疗人类革兰氏阴性菌败血症有用。
