Characterization of changes in plasma and tissue oxylipin levels in LPS and CLP induced murine sepsis
Characterization of changes in plasma and tissue oxylipin levels in LPS and CLP induced murine sepsis
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DOI：
10.1007/s00011-015-0897-7
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发表时间：
2016-02-01
影响因子：
6.7
通讯作者：
Schebb, Nils Helge
中科院分区：
文献类型：
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作者：
Willenberg, Ina;Rund, Katharina;Schebb, Nils Helge
本研究旨在全面探讨脂多糖（LPS）或盲肠结扎穿孔（CLP）诱导小鼠脓毒症过程中氧化脂素的变化。雄性C57 BL/6小鼠用LPS或CLP诱导脓毒症24小时后，采集血浆以及肝脏、肺、肾脏和心脏组织。采用LC-MS法检测血浆和组织中Oxylipin的含量，同时测定血浆中的临床生化指标和肾脏、肝脏中的白细胞介素（MCP-1和IL-6）水平，观察24 h肝功能指标的升高，结果表明两种模型均成功诱导了脓毒症。LPS诱导的脓毒症导致血浆PGE（2）（与对照组相比变化2,100%）和其他环氧合酶代谢物显著增加，而这种作用在CLP诱导的脓毒症中不太明显（PGE（2）增加97%）。血浆环氧-脂肪酸（FA）和羟基-FA和大多数的二羟基-FA在两种模型的败血症升高。组织氧脂素浓度的变化具有器官依赖性。在肺和肝组织中仅检测到少量变化，在肾脏中环氧-FA升高。在心脏组织中，羟基-FAs和环氧-FAs的水平降低的趋势被observed. Two小鼠模型的败血症的特点是在花生四烯酸（AA）级联反应的所有分支中形成的氧化脂质的变化。在LPS模型中更显著的作用使得该模型更适合于研究脓毒症中的AA级联及其药理学调节。
The present study aimed to comprehensively investigate the changes in oxylipins during murine sepsis induced by lipopolysaccharide (LPS) or cecal ligation and puncture (CLP).Twenty-four hours after induction of sepsis in male C57BL/6 mice by LPS or CLP, plasma and liver, lung, kidney and heart tissues were sampled. Oxylipin levels in plasma and tissue were quantified by means of LC-MS. Moreover, clinical chemistry parameters were determined in plasma and interleukin levels (MCP-1 and IL-6) were determined in kidney and liver.Elevation of liver function plasma parameters at 24 h revealed that both models were successful in the induction of sepsis. LPS induced sepsis resulted in a dramatic increase of plasma PGE(2) (2,100 % change in comparison to control) and other cyclooxygenase metabolites, whereas this effect was less pronounced in CLP induced sepsis (97 % increase of PGE(2)). Plasma epoxy-fatty acids (FAs) and hydroxy-FAs and most of the dihydroxy-FAs were elevated in both models of sepsis. Changes of tissue oxylipin concentrations were organ dependent. Only few changes were detected in the lung and liver tissue, epoxy-FAs were elevated in the kidney. In the heart tissue a trend towards lower levels of hydroxy-FAs and epoxy-FAs was observed.Both murine models of sepsis are characterized by changes of oxylipins formed in all branches of the arachidonic acid (AA) cascade. The more pronounced effects in the LPS model make this model more suitable for the investigation of the AA cascade and its pharmacological modulation in sepsis.