Deitch Edwin A, Lu Qi, Feketeova Eleonora, Hauser Carl J, Xu Da-Zhong
Department of Surgery, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, 07101-1709, USA.
J Trauma. 2004 Jan;56(1):105-10. doi: 10.1097/01.TA.0000054650.15837.1B.
We have previously documented that gut-derived lymph from rats subjected to trauma plus hemorrhagic shock (T/HS) is injurious to vascular endothelial cells and activates neutrophils (PMNs), two key events in postshock organ injury. Because T/HS leads to gut injury, intestinal bacterial overgrowth, and the loss of gut barrier function, the relative role of gut injury as opposed to intestinal bacterial overgrowth per se in the pathogenesis of biologically active intestinal lymph is unclear. We therefore studied whether mesenteric lymph can injure endothelial cells and/or active PMNs in an intestinal bacterial overgrowth model where there is no gut injury (monoassociation).
Bacterial overgrowth was established in male rats by treating the animals with 4 days of oral antibiotics followed by administration of a nonpathogenic, streptomycin-resistant strain of Escherichia coli C25. Mesenteric lymph was then collected from rats with normal flora and from E. coli C25 monoassociated rats. Its effects were tested on human umbilical vein endothelial cells (HUVECs) and human PMNs. As an additional control, lymph was collected from antibiotic-decontaminated rats that received antibiotics but were not colonized with E. coli C25.
As compared with medium, normal flora intestinal lymph, antibiotic-decontaminated lymph, or portal plasma from the monoassociated rats, mesenteric lymph from the monoassociated rats killed HUVECs and increased the permeability of a HUVEC monolayer. In contrast to the effects on HUVECs, lymph from the monoassociated rats did not increase PMN CD11b expression or prime PMNs for an augmented respiratory burst, as compared with lymph from the rats with normal flora or from antibiotic-decontaminated rats. The effects of lymph from the monoassociated rats was not caused by bacteria, because these lymph samples were sterile.
These results indicate that disruption of the normal intestinal microflora resulting in bacterial overgrowth with enteric bacilli may participate in the production of mesenteric lymph that is injurious to endothelial cells in shock, but this mechanism does not appear to be significantly involved in the activation of PMNs.
我们之前已证明，遭受创伤加失血性休克（T/HS）的大鼠的肠道源性淋巴液对血管内皮细胞具有损伤作用，并能激活中性粒细胞（PMN），这是休克后器官损伤中的两个关键事件。由于T/HS会导致肠道损伤、肠道细菌过度生长以及肠道屏障功能丧失，因此肠道损伤相对于肠道细菌过度生长本身在具有生物活性的肠道淋巴液发病机制中的相对作用尚不清楚。因此，我们研究了在没有肠道损伤的肠道细菌过度生长模型（单菌定植）中，肠系膜淋巴液是否会损伤内皮细胞和/或激活PMN。
通过给雄性大鼠口服抗生素4天，然后给予一株对链霉素耐药的非致病性大肠杆菌C25，建立大鼠肠道细菌过度生长模型。然后从具有正常菌群的大鼠和大肠杆菌C25单菌定植的大鼠中收集肠系膜淋巴液。测试其对人脐静脉内皮细胞（HUVEC）和人PMN的作用。作为额外对照，从接受抗生素但未被大肠杆菌C25定植的抗生素去污大鼠中收集淋巴液。
与培养基、正常菌群肠道淋巴液、抗生素去污淋巴液或单菌定植大鼠的门静脉血浆相比，单菌定植大鼠的肠系膜淋巴液可杀死HUVEC，并增加HUVEC单层的通透性。与对HUVEC的作用相反，与具有正常菌群的大鼠或抗生素去污大鼠的淋巴液相比，单菌定植大鼠的淋巴液不会增加PMN的CD11b表达或使PMN的呼吸爆发增强。单菌定植大鼠的淋巴液的作用不是由细菌引起的，因为这些淋巴液样本是无菌的。
这些结果表明，正常肠道微生物群的破坏导致肠道杆菌过度生长，可能参与了休克时对内皮细胞有损伤作用的肠系膜淋巴液的产生，但这种机制似乎并未显著参与PMN的激活。
