促炎及抗炎细胞因子在脓毒症小鼠肠道相关淋巴组织的表达  

Inflammation-promoting and anti-inflammatory cytokines gene expression in lymphocytes of gut-associated lymphoid tissue in septic mice

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

机构地区：[1]军事医学科学院附属医院,北京100039 [2]解放军总医院普通外科研究所,北京100853

出　　处：《军事医学科学院院刊》2005年第1期41-44,共4页Bulletin of the Academy of Military Medical Sciences

基　　金：国家自然科学基金资助项目(37670703)

摘　　要：目的:探讨脓毒症时小鼠肠道相关淋巴组织的淋巴细胞促炎及抗炎细胞因子的表达与全身炎症反应的关系.方法:NIH小鼠盲肠结扎穿孔(CLP)造成脓毒症,观察致伤后24 h存活率,并分别在致伤后3、12 h分离小鼠肠上皮间质淋巴细胞(IEL)、Peyer结节淋巴细胞(PPL)及肠系膜淋巴结淋巴细胞(MLNL).采用RT-PCR定量检测促炎细胞因子TNFα、IL-1β、IL-6和抗炎细胞因子IL-4在肠道相关淋巴组织中的表达.致伤后3、12 h分别抽取门静脉血进行细菌培养及鉴定.结果:致伤后24 h内,脓毒症组(CLP)存活率明显低于假手术组(SHAM)(1/10 vs 10/10),死亡高峰时间为致伤后14～16 h.促炎细胞因子TNFα、IL-1β、IL-6基因表达在指定时间点内,CLP组明显高于SHAM组(P<0.01);抗炎细胞因子IL4基因表达致伤后3 h同SHAM组比较无明显差异(P>0.05),但在致伤后12 h却明显低于致伤后3 h及SHAM组(P<0.01).CLP组门静脉血培养可见肠源性G-菌生长并随致伤时间的延长细菌培养阳性率明显增加,而SHAM组在指定时间点内未见细菌生长.结论:脓毒症时小鼠肠道相关淋巴组织细胞可见促炎细胞因子基因的过度表达而抗炎细胞因子基因明显低表达,促炎/抗炎细胞因子表达失衡,肠道的免疫屏障受损,肠源性细菌及毒素大量移位,加重了全身的炎症反应,表明肠道在脓毒症时可能是参与全身炎症反应的重要器官.Objective: To determine inflammation-promoting and anti-inflammatory cytokines gene expression in lymphocytes of gut-associated lymphoid tissue during sepsis. Methods: Male NIH mice were used in all experiments. Sepsis was induced by cecal ligation and puncture (CLP). The gut intraepithelial lymphocytes (IEL), Peyer’s patch lymphocytes (PPL) and mesenteric lymph node lymphocytes (MLNL) were harvested from the mice sacrficed 3 or 12 hours after CLP. Cytokines gene expression (TNFα, IL-1β, IL-6, IL-4) was examined by RT-PCR. Bacterial translocation was determined at the same indicated time points by culturing the portal vein blood. Results: Survival of CLP mice was 1/10 as compared to 10/10 of sham-operation group. The results of cytokine gene expression demonstrated that inflammation-promoting cytokines (TNFα, IL-1β, IL-6) had no significant change at 3 hours or 12 hours after CLP in sham-group. In contrast, anti-inflammatory cytokines (IL-4) had high expression in sham-operation group. TNFα, IL-1β, IL-6 gene expression were significantly increased and IL-4 gene were markedly decreased in CLP group. The portal blood culture showed no bacteria were present in sham-operation group. However, in CLP group, the bacteria were present in 83% of portal blood samples at 12 hours after CLP and 17% at 3 hours after CLP. Conclusion: Sepsis upregulated the inflammation-promoting cytokines (TNFα, IL-1β, IL-6) gene expression and downregulated the anti-inflammatory cytokine IL-4 expression in the lymphocytes of gut-associated lymphoid tissue. The unbalance between inflammation-promoting and anti-inflammatory cytokines might alter permeability of the intestinal mucosa and decrease the gut local defense. The gut immune barrier failure may promote the translocation of intraluminal bacteria and their toxin, which may be responsible for a fatal septic syndrome. The studies also showed that sepsis induces the gut to produce and liberate cytokines contributing to the development of systemic inflammatory response.

关 键 词：脓毒症 肠道 肠杆菌科感染 细胞因子类 基因表达 

分 类 号：R363[医药卫生—病理学]