骨桥蛋白与多微生物败血症小鼠模型中的炎症和死亡率相关。
Osteopontin is associated with inflammation and mortality in a mouse model of polymicrobial sepsis.
作者信息
Fortis S, Khadaroo R G, Haitsma J J, Zhang H
机构信息
Keenan Research Center for Biomedical Science, St. Michael's Hospital, Toronto, ON, Canada; Department of Anaesthesia, University of Toronto, Toronto, ON, Canada; Interdepartmental Division of Critical Care Medicine, University of Toronto, Toronto, ON, Canada; Department of Physiology, University of Toronto, Toronto, ON, Canada.
出版信息
Acta Anaesthesiol Scand. 2015 Feb;59(2):170-5. doi: 10.1111/aas.12422. Epub 2014 Oct 19.
BACKGROUND
Osteopontin (OPN) is a multifunctional glycoprotein with pro-inflammatory properties. In severe sepsis, levels of plasma OPN are significantly higher in non-survivors than in survivors. We hypothesized that OPN results in greater inflammation and worse outcome through modulation of endogenous glucocorticoid production in sepsis.
METHODS AND RESULTS
Sepsis was induced by cecal ligation and puncture (CLP) in wild type (WT) and OPN gene knockout (OPN(-/-) ) mice. In response to sepsis, the OPN(-/-) mice had lower levels of plasma cytokines and chemokines than the WT mice. The levels of corticosterone in plasma were similar between WT and OPN(-/-) sham animals but they increased 24 h after CLP induction in the WT mice, but not in the OPN(-/-) mice. The mortality rate was lower in the OPN(-/-) mice than in the WT mice.
CONCLUSION
OPN is associated with greater inflammatory response and increased mortality, despite the higher corticosterone levels in plasma. Corticosterone production is not impaired in the absence of OPN.
背景
骨桥蛋白（OPN）是一种具有促炎特性的多功能糖蛋白。在严重脓毒症中，非存活者的血浆OPN水平显著高于存活者。我们推测，OPN通过调节脓毒症中内源性糖皮质激素的产生，导致更严重的炎症反应和更差的预后。
方法与结果
通过盲肠结扎和穿刺（CLP）诱导野生型（WT）和OPN基因敲除（OPN(-/-)）小鼠发生脓毒症。对脓毒症的反应中，OPN(-/-)小鼠的血浆细胞因子和趋化因子水平低于WT小鼠。WT和OPN(-/-)假手术动物的血浆皮质酮水平相似，但在CLP诱导后24小时，WT小鼠的血浆皮质酮水平升高，而OPN(-/-)小鼠则未升高。OPN(-/-)小鼠的死亡率低于WT小鼠。
结论
尽管血浆皮质酮水平较高，但OPN与更强烈的炎症反应和更高的死亡率相关。在缺乏OPN的情况下，皮质酮的产生并未受损。
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