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

Effects of U75302,blocker of leukotriene B4 receptor 1,on cellular immunity and inflammation in septic mice

目的观察白三烯B4受体1(leukotriene B4receptor 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24h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。

Objective To observe the influence of U75302,blocker of leukotriene B4receptor 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 18male C57BL/6mice were randomly divided into sham group(n=6),CLP group(n=6)and CLP+ U75302intraperitoneal 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 24hafter surgery.Results Compared with the CLP group,CLP + U75302intraperitoneal injection group had significantly reduced blood TNF-αlevel(by 43%,P< 0.05),significantly increased IL-10level(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 B4receptor 1with U75302may decrease peripheral TNF-αlevel,increase IL-10level,and improve cellular immunity,which may be involved in inflammation of sepsis.