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白三烯B4受体1拮抗剂U75302对脓毒症小鼠细胞免疫与炎症反应的影响
李秀娟,王嘉锋,张燕,李金宝,邓小明*
0
(第二军医大学长海医院麻醉科, 上海 200433
*通信作者)
摘要:
目的 观察白三烯B4受体1(leukotriene B4 receptor 1,LTB4-BLT1)拮抗剂U75302对脓毒症小鼠免疫功能的影响,探讨阻断白三烯B4受体1在脓毒症治疗中的意义。方法 采用盲肠结扎穿孔术(cecal ligation and puncture,CLP)致脓毒症小鼠模型,将18只雄性C57BL/6小鼠随机分为假手术组(n=6)、 CLP组(n=6)、CLP+腹腔注射U75302组(n=6)。手术后24 h检测3组小鼠外周血中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)及白介素10(interleukin-10,IL-10)的水平,利用流式细胞术检测3组小鼠腹腔灌洗液中Gr-1+细胞的计数以及胸腺T淋巴细胞的凋亡情况。结果 与CLP组相比,CLP+腹腔注射U75302组小鼠外周血中的TNF-α水平降低约43%(P<0.05),IL-10水平升高约88%(P<0.05),腹腔Gr-1+细胞计数降低(P<0.05),胸腺T淋巴细胞凋亡比例减少(P<0.01)。结论 LTB4-BLT1拮抗剂U75302可降低外周血TNF-α水平、提高IL-10水平、改善细胞免疫,可能干预脓毒症的炎症反应。
关键词:  脓毒症  白三烯B4受体1  白三烯拮抗剂  细胞免疫  炎症
DOI:10.3724/SP.J.1008.2014.00246
投稿时间:2013-09-26修订日期:2013-11-29
基金项目:
Effects of U75302, blocker of leukotriene B4 receptor 1, on cellular immunity and inflammation in septic mice
LI Xiu-juan,WANG Jia-feng,ZHANG Yan,LI Jin-bao,DENG Xiao-ming*
(Department of Anesthesiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China
*Corresponding author.)
Abstract:
Objective To observe the influence of U75302, blocker of leukotriene B4 receptor 1, on immune function in septic mice, so as to explore the implication of blocking leukotriene B4 receptor 1 for treatment of sepsis. Methods Experimental sepsis model was induced by cecal ligation and puncture (CLP). A total of 18 male C57BL/6 mice were randomly divided into sham group (n=6), CLP group (n=6) and CLP + U75302 intraperitoneal injection group (n=6). The peripheral blood cytokine tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) levels, peritoneal lavage fluid Gr-1+ cell count and thymus T lymphocytes apoptosis were detected in mice of three groups 24 h after surgery. Results Compared with the CLP group, CLP + U75302 intraperitoneal injection group had significantly reduced blood TNF-α level (by 43%, P<0.05), significantly increased IL-10 level (by 88%, P<0.05), signficantly decreased Gr-1+ cell counts in peritoneal lavage fluid (P<0.05), and significantly decreased apoptosis of thymus T lymphocytes (P<0.01). Conclusion Blocking leukotriene B4 receptor 1 with U75302 may decrease peripheral TNF-α level, increase IL-10 level, and improve cellular immunity, which may be involved in inflammation of sepsis.
Key words:  sepsis  leukotriene B4 receptor 1  leukotriene antagonists  cellular immunity  inflammation