Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice.
Effect of hemorrhagic shock on gut barrier function and expression of stress-related genes in normal and gnotobiotic mice.
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失血性休克对正常和限生小鼠肠道屏障功能和应激相关基因表达的影响。
DOI：
10.1152/ajpregu.00278.2002
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Fink,MitchellP
中科院分区：
文献类型：
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作者：
Yang,Runkuan;Gallo,DavidJ;Baust,JeffreyJ;Watkins,SimonK;Delude,RussellL;Fink,MitchellP
我们试图确定肠源性微生物因素是否影响失血性休克和复苏(HS/R)时肝脏或肠道的炎症反应。常规小鼠和灵知生菌小鼠被不含革兰氏阴性菌的特定微生物群污染，接受假手术或HS/R，4h后取组织标本，检测回肠粘膜对FITC葡聚糖的通透性，以及肝和回肠粘膜稳态IL-6、诱导型一氧化氮合酶(INOS)、环氧合酶(COX)-2和肿瘤坏死因子(TNF)的mRNA水平。HS/R显著增加了常规小鼠的回肠粘膜通透性，而这种作用在生药动物中并不明显。HS/R显著增加了常规小鼠和生药小鼠肝脏中几个致炎基因的mRNA水平。HS/R可增加常规组小鼠回肠黏膜IL-6和COX-2mRNA的表达，但不能增加GNOTIONITY组小鼠回肠黏膜IL-6和COX-2mRNA的表达。如果给药小鼠感染大肠杆菌C25，HS/R可增加回肠粘膜通透性，上调IL-6和COX-2的表达。这些数据支持这样的观点，即肝脏对HS/R的炎症反应在很大程度上独立于肠道中潜在致病性革兰氏阴性细菌的存在，而对HS/R的局部粘膜反应在出血期和出血后不久受到管腔内微生物生态的深刻影响。
We sought to determine whether gut-derived microbial factors influence the hepatic or intestinal inflammatory response to hemorrhagic shock and resuscitation (HS/R). Conventional and gnotobiotic mice contaminated with a defined microbiota without gram-negative bacteria were subjected to either a sham procedure or HS/R. Tissue samples were obtained 4 h later for assessing ileal mucosal permeability to FITC dextran and hepatic and ileal mucosal steady-state IL-6, inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, and TNF mRNA levels. Whereas HS/R significantly increased ileal mucosal permeability in conventional mice, this effect was not apparent in gnotobiotic animals. HS/R markedly increased hepatic mRNA levels for several proinflammatory genes in both conventional and gnotobiotic mice. HS/R increased ileal mucosal IL-6 and COX-2 mRNA expression in conventional but not gnotobiotic mice. If gnotobiotic mice were contaminated withEscherichia coliC25, HS/R increased ileal mucosal permeability and upregulated expression of IL-6 and COX-2. These data support the view that the hepatic inflammatory response to HS/R is largely independent of the presence of potentially pathogenic gram-negative bacteria colonizing the gut, whereas the local mucosal response to HS/R is profoundly influenced by the microbial ecology within the lumen during and shortly after the period of hemorrhage.