Dual role of leukotriene B4 receptor type 1 in experimental sepsis
Dual role of leukotriene B4 receptor type 1 in experimental sepsis
复制标题
1 型白三烯 B4 受体在实验性脓毒症中的双重作用。
DOI：
10.1016/j.jss.2014.09.013
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发表时间：
2015-02-01
影响因子：
2.2
通讯作者：
Deng, Xiao-ming
中科院分区：
文献类型：
--
作者：
Li, Xiu-juan;Fu, Hong-yu;Deng, Xiao-ming
背景资料：不同研究结果存在争议，认为由白三烯B4（LTB 4）及其受体介导的白细胞募集可促进病原体清除，但也可能加重脓毒症时的器官损伤。本研究旨在比较BLT 1配体LTB 4及其拮抗剂U-75302对脓毒症的影响。将小鼠随机分为假手术组、CLP组、U-75302组和LTB 4组。在后三组中，CLP小鼠分别腹腔注射生理盐水、U-75302和LTB 4。结果：U-75302可减轻脓毒症大鼠的肺损伤，而LTB 4可加重肝损伤。LTB 4增加血浆白细胞介素-6、肿瘤坏死因子-α水平，U-75302增加血浆白细胞介素-10水平。LTB 4增加，而U-75302减少腹腔灌洗液中的中性粒细胞数量。LTB 4还增加了腹膜和脾脏CD 4（+）和CD 8（+）T细胞的数量。LTB 4组血液和腹腔灌洗液中细菌清除率显著提高。与载体相比，U-75302和LTB 4均未显著改变存活率，但LTB 4组的死亡率显著高于U-75302组。还进行了剂量反应分析，以比较U-75302和LTB 4在不同剂量下的作用。结论：U-75302可减轻脓毒症引起的器官损伤，而LTB 4可增加白细胞向感染部位的募集，但在多菌性脓毒症中，LTB 4的致死作用比U-75302强。(C)2015 Elsevier Inc. All rights reserved.
Background: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis.Methods: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate.Results: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-alpha, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice.Conclusions: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis. (C) 2015 Elsevier Inc. All rights reserved.