抗内毒素单抗下调脓毒症小鼠肠上皮细胞白细胞介素-1转换酶基因表达及逆转肠上皮细胞凋亡的作用  

Effects of anti-endotoxin monoclonal antibody on gut epithelial cells apoptosis and expression of inter-leukinl-converting enzyme in septic mice

作　　者：陈立军[1] 尉承泽[1] 宋旭华[2] 赵立[1] 孟宪钧[2] 

机构地区：[1]军事医学科学院附属307医院外一科,北京100039 [2]解放军总医院普通外科研究所

出　　处：《中华实验外科杂志》2003年第2期132-133,共2页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金资助项目(37670703)

摘　　要：目的观察抗内毒素单抗对脓毒症小鼠肠上皮细胞内诱导细胞凋亡的白细胞介素-1-转换酶(ICE)基因及细胞因子肿瘤坏死因子(TNF)-α、细胞介素(IL)-1β、IL-6基因表达的影响,判断其对防治脓毒症小鼠肠上皮细胞异常凋亡的功效。方法用盲肠结扎穿孔(CLP)造成小鼠脓毒症,动物分3组:实验组、对照组(假手术组)和治疗组。采用逆转录-聚合酶链反应(RT-PCR)方法定量检测ICE基因及细胞因子基因表达,琼脂糖凝胶电泳和流式细胞仪检测肠上皮细胞凋亡。结果抗内毒素单抗明显下调细胞因子TNF-αa、IL-1β、IL-6基因的表达并抑制了ICE基因表达,减少了肠上皮细胞凋亡数量,改善了动物的存活率。数据为ICE基因(0.37±0.08)、TNF-α(0.34±0.05)、IL-1β(0.49±0.17)、IL-6(0.43±0.14),与实验组相比差异有显著性(P<0.05)。结论抗内毒素单抗对脓毒症小鼠肠上皮细胞凋亡相关基因(ICE)及细胞因子基因表达具有明确的抑制作用,对脓毒症小鼠肠上皮完整性(机械屏障)有保护作用。Objective To investigate the effects of anti-LPS monoclonal antibody (MAb) on the gut epithelial cells apoptosis and expression of interleukin-1-converting enzyme (ICE) mRNA in septic mice. Methods Sepsis were induced in mice by cecal ligation and puncture (CLP). Gut epithelial cells apoptosis was assessed by DNA gel electrophoresis and flow cytometry. TNF-α, IL-1β, IL-6 and ICE genes expression was detected quantitatively by RT-PCR. Results Sepsis markedly induced TNF-α, IL-1β, IL-6 and ICE genes expression and increased the gut epithelial cells apoptosis. The number of apoptot-ic cells was correlated closely with the level of ICE mRNA expression. Anti-LPS MAb significantly improved the animals survival, downregulated the TNF-α, IL-1β, IL-6 genes expression, inhibited ICE mRNA expression and decreased the epithelial cells apoptosis. Conclusion Anti-LPS MAb could obviously downregulate the TNF-α, IL-1β, IL-6, ICE genes expression, and effectively reduce apoptosis in the gut epithelial cells in septic mice.

关 键 词：抗内毒素单抗 脓毒症 小鼠 肠上皮细胞 白细胞介素-1 转换酶 基因表达 细胞凋亡 单克隆抗体 

分 类 号：R631[医药卫生—外科学]