Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome.
Critical roles of platelets in lipopolysaccharide-induced lethality: effects of glycyrrhizin and possible strategy for acute respiratory distress syndrome.
复制标题
DOI：
10.1016/j.intimp.2004.11.004
复制
发表时间：
2005-03
影响因子：
5.6
通讯作者：
Endo Y
中科院分区：
文献类型：
--
作者：
Yu Z;Ohtaki Y;Kai K;Sasano T;Shimauchi H;Yokochi T;Takada H;Sugawara S;Kumagai K;Endo Y
在静脉注射脂多糖（LPS）到小鼠体内的几分钟内，血小板聚集，主要在肺中。在较高剂量下，LPS诱导快速休克（10分钟内），导致1小时内死亡。这种类型的休克与所谓的内毒素休克不同，内毒素休克在几小时或更长时间后出现休克体征和死亡。在这里，我们发现，血小板耗竭（单克隆抗血小板抗体）防止LPS诱导的快速休克，但增加延迟致死率。在日本，甘草素（GL）是一种从甘草中分离出来的化合物，每天缓慢地静脉输注到慢性丙型肝炎患者体内。在LPS注射前不久（或同时）单次静脉注射GL（200 mg/kg或更低）可减少肺血小板蓄积和快速休克的严重程度，并防止早期和晚期死亡。GL本身在400 mg/kg剂量下未导致小鼠外观或活动出现可检测到的异常。腹腔注射阿司匹林或地塞米松对LPS诱导的血小板反应和致死率仅有轻微影响。这些结果表明，血小板在LPS诱导的快速型和延迟型休克的发生中起重要作用。虽然GL抑制血小板反应和延迟致死的机制仍有待澄清，GL可能提供一种缓解脓毒症急性呼吸窘迫综合征的策略。我们的结果也可能支持Cinatl等人的建议[Cinatl J，Morgenstern B，Bauer G，Chandra P，Ravenau H，Doerr HW.甘草素，甘草的活性成分，与SARS相关冠状病毒的复制。Lancet 2003; 361：2045-6.] GL可能是一种有效的抗SARS药物。
Within a few minutes of an intravenous injection of a lipopolysaccharide (LPS) into mice, platelets accumulate, largely in the lung. At higher doses, LPS induces rapid shock (within 10 min), leading to death within 1 h. This type of shock differs from so-called endotoxin shock, in which shock signs and death occur several hours or more later. Here, we found that platelet depletion (by a monoclonal anti-platelet antibody) prevented LPS-induced rapid shock, but increased delayed lethality. In Japan, glycyrrhizin (GL), a compound isolated from licorice, is daily and slowly infused intravenously into chronic hepatitis C patients. A single bolus intravenous injection into mice of GL (200 mg/kg or less) shortly before (or simultaneously with) LPS injection reduced the pulmonary platelet accumulation and the severity of the rapid shock, and prevented death in both the early and later periods. GL itself, at 400 mg/kg, produced no detectable abnormalities in the appearance or activity of mice. Intraperitoneal injection of aspirin or dexamethasone had only marginal effects on LPS-induced platelet responses and lethality. These results suggest that platelets play important roles in the development of both the rapid and delayed types of shock induced by LPS. Although the mechanism by which GL suppresses platelet responses and delayed lethality remains to be clarified, GL might provide a strategy for alleviating the acute respiratory distress syndrome seen in sepsis. Our results may also support the proposal by Cinatl et al. [Cinatl J, Morgenstern B, Bauer G, Chandra P, Ravenau H, Doerr HW. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus. Lancet 2003; 361: 2045–6.] that GL may be an effective drug against severe acute respiratory syndrome.
登录
查看更多内容
DOI：
10.1902/annals.1998.3.1.151
发表时间：
1998-07-01
期刊：
Annals of periodontology
影响因子：
--
作者：
Herzberg, M C;Weyer, M W
通讯作者：
Weyer, M W
影响因子：
3.2
作者：
Mattson, DL
通讯作者：
Mattson, DL
影响因子：
15.3
作者：
LEHMANN, V;FREUDENBERG, MA;GALANOS, C
通讯作者：
GALANOS, C
DOI：
10.1073/pnas.76.11.5939
发表时间：
1979-01-01
影响因子：
11.1
作者：
GALANOS, C;FREUDENBERG, MA;REUTTER, W
通讯作者：
REUTTER, W
影响因子：
2.6
作者：
Fujisawa, Y;Sakamoto, M;Nishioka, K
通讯作者：
Nishioka, K