LIPID-X AMELIORATES PULMONARY-HYPERTENSION AND PROTECTS SHEEP FROM DEATH DUE TO ENDOTOXIN
LIPID-X AMELIORATES PULMONARY-HYPERTENSION AND PROTECTS SHEEP FROM DEATH DUE TO ENDOTOXIN
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DOI：
10.1128/iai.55.10.2471-2476.1987
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发表时间：
1987-10-01
影响因子：
3.1
通讯作者：
PROCTOR, RA
中科院分区：
文献类型：
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作者：
GOLENBOCK, DT;WILL, JA;PROCTOR, RA
Lipid X（2，3-diacylglucosamine-1-phosphate）是一种新型的脂质A的单糖前体，具有内毒素的某些生理活性，但毒性很小。为了确定脂质X是否会干扰内毒素的毒性作用，我们用100或200 μ g脂质X/kg体重预处理绵羊，然后用潜在致死剂量的大肠杆菌内毒素（20 μ g/kg）攻击它们。21只绵羊接受了肺动脉导管插入术，并在7小时内监测肺动脉压、温度、pH值、氧分压、二氧化碳分压、血压和细胞计数的变化。对照组动物的总体死亡率为37%，而预处理组动物为5.3%。用100 μ g脂质X/kg预处理的13只动物无一死亡。生存率差异有统计学意义（P < 0.05）。用100 μ g脂质X/kg预处理的动物在内毒素诱导的肺动脉高压的第1和第2阶段期间具有显著较低的肺动脉压。较高剂量的脂质X，200 μ g/kg，产生肺动脉高压。可能因为脂质X是脂质A的亚基，脂质X显示部分致热效应，同时也降低完全脂多糖（LPS）的致热活性。脂质X不能预防内毒素诱导的中性粒细胞减少症或对LPS的中度低血压。Lipid X是一种潜在的原型化合物，用于新型化疗，旨在阻断细菌败血症期间LPS的有害作用。
Lipid X (2,3-diacylglucosamine-1-phosphate) is a novel monosaccharide precursor of lipid A that has some of the physiologic activities of endotoxin but little toxicity. To determine whether lipid X would interfere with the toxic effects of endotoxin, we pretreated sheep with either 100 or 200 .mu.g of lipid X per kg of body weight and then challenged them with a potentially fatal dose of Escherichia coli endotoxin (20 .mu.g/kg). Twenty-one sheep underwent pulmonary artery catheterization and were monitored for changes in pulmonary artery pressure, temperature, pH, partial O2 pressure, partial CO2 pressure, blood pressure, and cell counts over 7 h. Overall mortality for control animals was 37% versus 5.3% for pretreated animals. None of the 13 animals pretreated with 100 .mu.g of lipid X per kg died. These differences in survival were significant (P < 0.05). Animals pretreated with 100 .mu.g of lipid X per kg had significantly lower pulmonary artery pressure during both phases 1 and 2 of endotoxin-induced pulmonary artery hypertension. A higher dose of lipid X, 200 .mu.g/kg, produced pulmonary hypertension. Perhaps because lipid X is a subunit of lipid A, lipid X shows a partial pyrogenic effect while also decreasing the pyrogenic activity of complete lipopolysaccharide (LPS). Lipid X did not prevent endotoxin-induced neutropenia or moderate hypotension in response to LPS. Lipid X is a potential prototype compound for a new type of chemotherapy directed at blocking the harmful effects of LPS during bacterial septicemia.