Pellicane J V, Gore D C, DeMaria E J
Department of Surgery, Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
J Surg Res. 1994 Apr;56(4):361-6. doi: 10.1006/jsre.1994.1056.
Although C3H/HeJ mice, characterized by a genetic deficiency in macrophage cytokine release in response to endotoxin, have been studied extensively to gain insight into the possible role of various cytokines in sepsis, few past studies have examined the physiologic response to hemorrhagic shock in this "endotoxin-resistant" strain. We utilized a fixed-volume model of hemorrhagic shock and two different levels of hemorrhage severity (50 and 67% blood volume) to compare C3H/HeJ mice to normal C3H/HeN mice. An additional group of endotoxin-sensitive C3H/HeN mice were treated with 2.5 mg/kg of anti-tumor necrosis factor (TNF) antibody to define the possible role of TNF in shock physiology. Hematocrit, circulating neutrophils, and plasma glucose and lactate concentrations were measured following hemorrhage. TNF increased significantly following hemorrhage in normal mice but did not increase in C3H/HeJ mice or in C3H/HeN mice treated with anti-TNF antibody. No difference between groups was identified in hematocrit, circulating neutrophils, or glucose. Whereas plasma lactate increased significantly by 30 min in all groups, lactate returned to baseline levels in C3H/HeJ mice at 60 min, but remained persistently elevated in C3H/HeN mice and in C3H/HeN mice treated with anti-TNF antibody. The data demonstrate attenuated lactate accumulation in C3H/HeJ mice following hemorrhage. Inhibition of circulating TNF activity with anti-TNF antibody failed to reproduce this late decrease in plasma lactate in normal mice. The data suggest that macrophage products other than TNF known to be deficient in C3H/HeJ mice contribute to anaerobic metabolism in hemorrhagic shock.
尽管C3H/HeJ小鼠因对内毒素反应时巨噬细胞细胞因子释放存在基因缺陷而被广泛研究，以深入了解各种细胞因子在脓毒症中可能发挥的作用，但过去很少有研究考察这种“内毒素抵抗”品系对失血性休克的生理反应。我们采用固定容量的失血性休克模型和两种不同程度的出血严重性（失血50%和67%血容量），将C3H/HeJ小鼠与正常的C3H/HeN小鼠进行比较。另外一组内毒素敏感的C3H/HeN小鼠用2.5mg/kg的抗肿瘤坏死因子（TNF）抗体进行处理，以确定TNF在休克生理学中的可能作用。在出血后测量血细胞比容、循环中的中性粒细胞以及血浆葡萄糖和乳酸浓度。正常小鼠出血后TNF显著增加，但C3H/HeJ小鼠或用抗TNF抗体处理的C3H/HeN小鼠中TNF没有增加。在血细胞比容、循环中的中性粒细胞或葡萄糖方面，未发现各组之间存在差异。虽然所有组的血浆乳酸在30分钟时均显著增加，但C3H/HeJ小鼠的乳酸在60分钟时恢复到基线水平，但C3H/HeN小鼠和用抗TNF抗体处理的C3H/HeN小鼠中的乳酸仍持续升高。数据表明，C3H/HeJ小鼠出血后乳酸积累减弱。用抗TNF抗体抑制循环中的TNF活性未能重现正常小鼠血浆乳酸的这种后期下降情况。数据表明除TNF外已知在C3H/HeJ小鼠中缺乏的巨噬细胞产物在失血性休克中有助于无氧代谢。
