HEMORRHAGIC-SHOCK IN ENDOTOXIN-RESISTANT MICE - IMPROVED SURVIVAL UNRELATED TO DEFICIENT PRODUCTION OF TUMOR-NECROSIS-FACTOR
HEMORRHAGIC-SHOCK IN ENDOTOXIN-RESISTANT MICE - IMPROVED SURVIVAL UNRELATED TO DEFICIENT PRODUCTION OF TUMOR-NECROSIS-FACTOR
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DOI：
10.1097/00005373-199311000-00012
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发表时间：
1993-11-01
影响因子：
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通讯作者：
LEE, RB
中科院分区：
文献类型：
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作者：
DEMARIA, EJ;PELLICANE, JV;LEE, RB
尽管肿瘤坏死因子（TNF）与脓毒症引起的死亡率有关，但其在出血性休克（HS）病理生理学中的作用仍不明确。我们研究了三组急性麻醉的小鼠进行HS，以确定肿瘤坏死因子在HS死亡率的作用。各组均在肝素化后通过动脉出血4 mL/100 g体重开始休克，随后在1 h用生理盐水12 mL/100 g体重复苏。将C3 H/HeJ小鼠（n = 14）与密切相关的产生TNF的C3 H/HeN品系（n = 18）进行比较，C3 H/HeJ小鼠（n = 14）的特征在于响应于内毒素的巨噬细胞产生TNF和其他细胞因子的遗传缺陷。第二组C3 H/HeN小鼠通过在HS之前用2.5mg/kg抗鼠TNF抗体（Ab）预处理而被动免疫TNF。与在C3 H/HeN对照中HS后测量的高TNF水平相反，在C3 H/HeJ小鼠中HS后TNF不可检测。与C3 H/HeN对照组相比，C3 H/HeJ小鼠的五天存活率和存活时间显著更高。C3 H/HeN小鼠的抗TNF Ab预处理消除了TNF的增加，但没有改善存活率。这些数据表明严重HS后TNF缺陷型C3 H/HeJ小鼠的存活率显著改善。然而，改善的生存率似乎不是由于TNF产生不足，因为Ab预处理没有降低HS死亡率。C3 H/HeJ小鼠存活率的提高表明，除TNF以外的细胞因子可能在HS的病理生理学中发挥作用。
Although tumor necrosis factor (TNF) has been implicated in sepsis-induced mortality, its role in the pathophysiology of hemorrhagic shock (HS) remains ill defined. We studied three groups of acutely anesthetized mice undergoing HS to determine the role of TNF in HS mortality. Shock was initiated in each group after heparinization by arterial bleeding of 4 mL/100 g body weight followed by 12 mL/100 g body weight resuscitation with normal saline at 1 hour. The C3H/HeJ mice (n = 14), characterized by a genetic defect in macrophage production of TNF and other cytokines in response to endotoxin, were compared with the closely related C3H/HeN strain (n = 18), which do produce TNF. A second group of C3H/HeN mice were passively immunized to TNF by pretreatment with 2.5 mg/kg anti-murine TNF antibody (Ab) before HS. In contrast to the high TNF levels measured following HS in C3H/HeN controls, post-HS TNF was undetectable in C3H/HeJ mice. Five-day survival rate and survival time were significantly greater in C3H/HeJ mice when compared with C3H/HeN controls. Anti-TNF Ab pretreatment of C3H/HeN mice abolished the increase in TNF but did not improve survival. The data demonstrate a striking improvement in survival of TNF-deficient C3H/HeJ mice following severe HS. However, the improved survival does not appear to result from deficient TNF production, since Ab pretreatment did not decrease HS mortality. The improved survival in C3H/HeJ mice suggests that cytokines other than TNF may play a role in the pathophysiology of HS.