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弹性蛋白酶抑制剂艾格林对内毒素血症绵羊模型无效。

The elastase-inhibitor eglin has no effect in an ovine model of endotoxemia.

作者信息

Redl H, Schlag G, Vogl C, Schiesser A, Paul E, Thurnher M, Junger W, Traber L D, Traber D L

机构信息

Ludwig-Boltzmann-Institut für experimentelle Traumatologie, Wien.

出版信息

Biol Chem Hoppe Seyler. 1988 May;369 Suppl:153-6.

PMID:3060136
Abstract

Small doses of endotoxin have been shown to induce pulmonary microvascular injury in sheep, possibly by the action of granulocytes. Eglin, a potent inhibitor of neutrophil elastase, was tested in an ovine model of endotoxemia. The experiment was performed in 12 unanesthetized chronically instrumented sheep with a lung lymph preparation. Endotoxin (S. abort. equii) was infused at 24 ng/(kg x h) with application of 20 mg/kg eglin 1 h before endotoxin in the treatment group and followed by 5 mg/(kg x h). No significant improvement due to the treatment was seen for either cardiovascular status (pulmonary and systemic vascular resistance) or permeability changes in the lung (lymph flow and lymph/plasma protein ratio), although sufficient eglin concentrations were achieved in plasma and lymph. The lack of an effect of eglin might be because higher concentrations are needed to block elastase-like activity of ovine granulocytes or because of a minor role for neutrophil elastase in this shock model.

摘要

小剂量内毒素已被证明可在绵羊中诱发肺微血管损伤,可能是通过粒细胞的作用。埃格林是一种有效的中性粒细胞弹性蛋白酶抑制剂,在内毒素血症的绵羊模型中进行了测试。实验在12只未麻醉的、长期植入仪器的绵羊身上进行,这些绵羊有肺淋巴制备装置。治疗组在注射内毒素前1小时给予20mg/kg埃格林,然后以5mg/(kg·h)的剂量输注内毒素(马流产沙门氏菌),剂量为24ng/(kg·h)。尽管在血浆和淋巴中达到了足够的埃格林浓度,但治疗对心血管状态(肺和全身血管阻力)或肺通透性变化(淋巴流量和淋巴/血浆蛋白比率)均未产生显著改善。埃格林缺乏效果可能是因为需要更高的浓度来阻断绵羊粒细胞的弹性蛋白酶样活性,或者是因为中性粒细胞弹性蛋白酶在这种休克模型中的作用较小。

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