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预防内毒素血症:血浆置换及多粘菌素B特异性吸附的大鼠模型

Protection from endotoxemia: a rat model of plasmapheresis and specific adsorption with polymyxin B.

作者信息

Cohen J, Aslam M, Pusey C D, Ryan C J

出版信息

J Infect Dis. 1987 Apr;155(4):690-5. doi: 10.1093/infdis/155.4.690.

DOI:10.1093/infdis/155.4.690
PMID:3029243
Abstract

Polymyxin B (PB), a cyclic polypeptide antibiotic, has potent antiendotoxin properties but is associated with significant toxicity when given parenterally. As an alternative, PB was immobilized on a solid phase (Sepharose 4B; Pharmacia, Uppsala, Sweden), and a system of plasmapheresis was developed in the conscious rat, with specific on-line plasma adsorption of endotoxin by a PB-Sepharose column. PB-Sepharose columns removed 94% of a challenge dose of 5 micrograms of endotoxin in vitro. Rats were pretreated with lead acetate so that they were sensitized to endotoxin and then given 10 micrograms of endotoxin/kg intraarterially. After 15 min plasmapheresis was begun and continued for 90 min. Animals whose plasma was perfused over PB-Sepharose were protected from endotoxin-induced leukopenia (P less than .01), thrombocytopenia (P less than .001), and death (four of four survivors compared with none of four controls). Thus plasmapheresis with on-line removal of endotoxin is a safe and highly effective means of protecting animals from the effects of endotoxemia.

摘要

多粘菌素B(PB)是一种环状多肽抗生素,具有强大的抗内毒素特性,但经肠胃外给药时会产生显著毒性。作为一种替代方法,将PB固定在固相载体(琼脂糖凝胶4B;瑞典乌普萨拉法玛西亚公司)上,并在清醒大鼠中开发了一种血浆置换系统,通过PB-琼脂糖凝胶柱对血浆中的内毒素进行特异性在线吸附。PB-琼脂糖凝胶柱在体外可去除5微克内毒素攻击剂量的94%。用醋酸铅对大鼠进行预处理,使其对内毒素敏感,然后动脉内给予10微克内毒素/千克。15分钟后开始血浆置换,并持续90分钟。血浆经PB-琼脂糖凝胶柱灌注的动物可免受内毒素诱导的白细胞减少(P<0.01)、血小板减少(P<0.001)和死亡(四只存活四只,而四个对照组无一存活)。因此,在线去除内毒素的血浆置换是保护动物免受内毒素血症影响的一种安全且高效的方法。

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