银杏内酯B对CLP诱导脓毒症小鼠的保护作用  

Protective effect of ginkgolide B on CLP-induced septic mice

作　　者：王晓东[1] 宋兵[2] 曾耀英[1] 

机构地区：[1]暨南大学组织移植与免疫实验中心,广东广州510632 [2]广州医学院第三附属医院,广东广州510150

出　　处：《中国病理生理杂志》2012年第10期1868-1872,共5页Chinese Journal of Pathophysiology

基　　金："973"国家重点基础研究资助项目(No.2006CB504201;No.2004CB720100);广东省自然科学基金资助项目(No.2006B36030016);广州市科技局科技攻关重点资助项目(No.2006Z-E0091)

摘　　要：目的:银杏内酯B(GB)是已知的天然而强效的血小板激活因子受体拮抗剂。本实验通过研究GB对盲肠结扎穿孔(CLP)诱导的脓毒症小鼠的存活、外周血一氧化氮(NO)、活性氧簇(ROS)及细胞因子TNF-α、IL-1β、IL-6和IL-10的影响来评价其对脓毒症的免疫调节效果。方法:采用CLP的标准化程序建立小鼠脓毒症模型,术前30 min对药物组模型小鼠进行GB(10μg/g)预处理;统计存活率;以Griess法检测小鼠外周血NO水平;以H2DCFDA标记结合流式细胞术检测外周血ROS水平;以流式细胞微球阵列法与ELISA法检测外周血细胞因子水平。结果:CLP手术后24 h,小鼠胸腺和脾脏萎缩明显,外周血炎症介质NO和ROS及细胞因子TNF-α、IL-1β、IL-6和IL-10的水平均显著上升,术后5 d内CLP模型小鼠全部死亡,而10μg/g GB于术前30 min预处理,能缓解胸腺和脾脏萎缩,有效抑制炎症介质与炎性细胞因子风暴,显著提高脓毒症存活率。结论:GB预处理能显著降低CLP小鼠死亡率,下调外周血炎症介质NO和ROS及细胞因子TNF-α、IL-1β、IL-6和IL-10的水平,对脓毒症小鼠有明显的保护作用。AIM： To explore the potential immunomodulatory effect and related mechanisms of ginkgolide B （ GB）, a known potent antagonist of platelet - activating factor receptor, on the pathological process of sepsis. METHODS： The experimental sepsis model was established by a standardized procedure of cecal ligation and puncture （CLP）. GB treatment （10 μg/g） was given to the CLP mice 30 min before the surgical operation. The survival rate was observed every day for 3 weeks. The NO content in the serum was measured by Griess assay. The ROS level in the blood was deter- mined by H2 DCFDA labeling and flow cytometry. The inflammatory cytokines in the serum were detected by the methods of cytometric bead array and ELISA. RESULTS： The thymus and spleen of the mice significantly atrophied, and the levels of NO, ROS, TNF -α, IL - 1β, IL - 6 and IL - 10 in the blood were dramatically elevated 24 h after CLP. All the CLP mice died in 5 days. However, treatment with 10 μg/g of GB 30 min before CLP remarkably enhanced the indexes of thymus and spleen, inhibited the storm of inflammatory mediators and cytokines, and improved the survival rate. CONCLUSION ： The protective effect of GB on CLP - induced experimental sepsis indicates that GB is a candidate of natural immunomodulator for treating sepsis.

关 键 词：银杏内酯B 脓毒症 存活 细胞因子类 

分 类 号：R392.32[医药卫生—免疫学]