Role of tumor necrosis factor-alpha in acute hypovolemic hemorrhagic shock in rats.
Role of tumor necrosis factor-alpha in acute hypovolemic hemorrhagic shock in rats.
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肿瘤坏死因子-α 在大鼠急性低血容量失血性休克中的作用。
DOI：
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发表时间：
1994
影响因子：
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通讯作者：
A. Caputi
中科院分区：
文献类型：
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作者：
B. Zingarelli;F. Squadrito;D. Altavilla;Gioacchino Calapai;M. D. Rosa;A. Caputi
通过从髂导管间歇性抽血直至平均动脉压（MAP）下降并稳定在20-30mmHg范围内，在雄性麻醉大鼠中诱导失血性休克。然后评估存活率、MAP以及肿瘤坏死因子-α（TNF-α）的血清和巨噬细胞水平。此外，在离体研究中，研究了失血性休克大鼠的主动脉环对去氧肾上腺素（PE；1 nM 至 10 microM）的反应性。出血前3小时静脉注射抗TNF-α抗体（抗TNF-α；2mg/kg）或媒介物（磷酸盐缓冲盐水，1ml/kg）。遭受失血性休克的媒介物治疗大鼠表现出急性和严重的低血压（MAP = 20-30 mmHg）以及高水平的血清（790 +/- 47 pg/ml）和巨噬细胞（78 +/- 9 pg/ml）TNF-α，并在30分钟内死亡。此外，与一组假电击大鼠的主动脉的反应性相比，电击大鼠的主动脉对 PE 表现出明显的收缩性低下。抗 TNF-α 给药显着提高低血容量休克大鼠的存活率和 MAP。此外，主动脉环对 PE 的低反应性显着恢复。因此，这些数据表明 TNF-α 是低血容量失血性休克病理生理学中的重要介质，并且它可能至少部分地导致该实验性循环休克的血管反应性低下。
Hemorrhagic shock was induced in male anesthetized rats by intermittently withdrawing blood from an iliac catheter until mean arterial blood pressure (MAP) fell and stabilized within the range of 20-30 mmHg. Survival rate, MAP, and serum and macrophage levels of tumor necrosis factor-alpha (TNF-alpha) were then evaluated. Furthermore, in ex vivo studies, the responsiveness to phenylephrine (PE; 1 nM to 10 microM) was investigated in aortic rings from hemorrhagic shocked rats. Antibodies raised against TNF-alpha (anti-TNF-alpha; 2 mg/kg) or vehicle (phosphate-buffered saline, 1 ml/kg) were injected intravenously 3 h before the bleeding. Vehicle-treated rats, subjected to hemorrhagic shock, exhibited acute and serious hypotension (MAP = 20-30 mmHg) and high levels of serum (790 +/- 47 pg/ml) and macrophage (78 +/- 9 pg/ml) TNF-alpha and died within 30 min. Moreover, aortas from shocked rats showed a marked hypocontractility to PE compared with the reactivity of aortas from a group of sham shocked rats. Anti-TNF-alpha administration significantly improved survival rate and MAP in hypovolemic shocked rats. Furthermore, the hyporesponsiveness to PE was significantly restored in aortic rings. Therefore, these data suggest that TNF-alpha is an important mediator in the pathophysiology of hypovolemic hemorrhagic shock and it might be responsible, at least in part, for the vascular hyporeactivity of this experimental circulatory shock.