Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.
Decrease of plasma platelet-activating factor acetylhydrolase activity in lipopolysaccharide induced mongolian gerbil sepsis model.
复制标题
脂多糖诱导蒙古沙鼠败血症模型血浆血小板激活因子乙酰水解酶活性的降低
DOI：
10.1371/journal.pone.0009190
复制
发表时间：
2010-02-12
期刊：
影响因子：
3.7
通讯作者：
Zhao G
中科院分区：
文献类型：
--
作者：
Yang J;Xu J;Chen X;Zhang Y;Jiang X;Guo X;Zhao G
血小板活化因子（PAF）在脓毒症的发病机制中起重要作用，除严重钩端螺旋体病引起的脓毒症外，脓毒症患者血浆PAF乙酰水解酶（pPAF-AH）水平均降低。通常，在脂多糖（LPS）诱导的叙利亚仓鼠和大鼠脓毒症模型中观察到pPAF-AH活性增加，而在不同的研究中报道了小鼠模型的矛盾效应。本研究以C57 BL/6小鼠和蒙古沙鼠为实验动物，观察了LPS对pPAF-AH活性的影响。经LPS治疗后，长爪沙鼠模型的临床表现与C57 BL/6小鼠脓毒症模型相似。LPS诱导C57 BL/6小鼠pPAF-AH活性升高，蒙古沙鼠pPAF-AH活性降低，与人类脓毒症相似。因此，在LPS诱导的啮齿类动物脓毒症模型中，只有长爪沙鼠可用于研究pPAF-AH与人类脓毒症发病机制的关系。该模型的正确应用可能使人们能够阐明重组人pPAF-AH治疗脓毒症的II期和III期临床试验结果相互矛盾的潜在机制。
Platelet-activating factor (PAF) plays an important role in the pathogenesis of sepsis, and the level of plasma PAF acetylhydrolase (pPAF-AH), which inactivates PAF, decreases in sepsis patients except for the sepsis caused by severe leptospirosis. Usually, increase of pPAF-AH activity was observed in lipopolysaccharide (LPS)-induced Syrian hamster and rat sepsis models, while contradictory effects were reported for mouse model in different studies. Here, we demonstrated the in vivo effects of LPS upon the change of pPAF-AH activity in C57BL/6 mice and Mongolian gerbils. After LPS-treatment, the clinical manifestations of Mongolian gerbil model were apparently similar to that of C57BL/6 mouse sepsis model. The pPAF-AH activity increased in C57BL/6 mice after LPS induction, but decreased in Mongolian gerbils, which was similar to that of the human sepsis. It thus suggests that among the LPS-induced rodent sepsis models, only Mongolian gerbil could be used for the study of pPAF-AH related to the pathogenesis of human sepsis. Proper application of this model might enable people to clarify the underline mechanism accounted for the contradictory results between the phase II and phase III clinical trials for the administration of recombinant human pPAF-AH in the sepsis therapy.
登录
查看更多内容
影响因子：
8.8
作者：
GRAHAM, RM;STEPHENS, CJ;TAYLOR, RR
通讯作者：
TAYLOR, RR
影响因子：
8.8
作者：
Schuster, DP;Metzler, M;Pribble, J
通讯作者：
Pribble, J
血小板激活因子乙酰水解酶的血清活性是钩端螺旋体病肺出血的潜在临床标志物
影响因子：
3.7
作者：
Yang J;Zhang Y;Xu J;Geng Y;Chen X;Yang H;Wang S;Wang H;Jiang X;Guo X;Zhao G
通讯作者：
Zhao G
影响因子：
4.8
作者：
Howard, KM;Olson, MS
通讯作者：
Olson, MS
影响因子：
8.8
作者：
Zimmerman, GA;McIntyre, TM;Stafforini, DM
通讯作者：
Stafforini, DM