The endogenous bacteria alter gut epithelial apoptosis and decrease mortality following Pseudomonas aeruginosa pneumonia.
The endogenous bacteria alter gut epithelial apoptosis and decrease mortality following Pseudomonas aeruginosa pneumonia.
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内源性细菌会改变肠道上的肠道凋亡，并在铜绿假单胞菌肺炎降低死亡率。
DOI：
10.1097/shk.0b013e31826e47e8
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发表时间：
2012-11
期刊：
影响因子：
--
通讯作者：
Coopersmith CM
中科院分区：
文献类型：
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作者：
Fox AC;McConnell KW;Yoseph BP;Breed E;Liang Z;Clark AT;O'Donnell D;Zee-Cheng B;Jung E;Dominguez JA;Dunne WM;Burd EM;Coopersmith CM
内源性细菌已被假设在危重病的病理生理学中起重要作用，尽管它们在脓毒症中的作用知之甚少。本研究的目的是确定肠道细菌如何改变宿主对脓毒症的反应。使常规和无菌（GF）C57 B1/6小鼠经受铜绿假单胞菌肺炎。所有GF小鼠在两天内死亡，而44%的常规小鼠存活7天（p=0.001）。在GF小鼠中将细菌剂量稀释10倍，导致GF和常规小鼠的存活率相似。当对具有相似死亡率的动物进行肠完整性分析时，GF小鼠的肠上皮细胞凋亡水平较低，但增殖和肠通透性水平相似。与常规小鼠相比，GF小鼠的BAL液中TNF和IL-1β水平显著降低，而全身细胞因子产生无变化。在常规条件下，脓毒症揭示了淋巴细胞对肠上皮细胞凋亡的控制，因为脓毒症诱导Rag-1−/−小鼠肠道细胞凋亡的增加比野生型（WT）小鼠更大。然而，在一组单独的实验中，脓毒症GF Rag-1−/−小鼠和脓毒症GF WT小鼠之间的肠道细胞凋亡相似。这些数据表明，内源性细菌在介导肺炎诱导的脓毒症的死亡率中起保护作用，可能通过改变肠细胞凋亡和局部促炎反应介导。此外，脓毒症诱导的淋巴细胞依赖性肠道上皮细胞凋亡增加似乎是由内源性细菌介导的。
The endogenous bacteria have been hypothesized to play a significant role in the pathophysiology of critical illness, although their role in sepsis is poorly understood. The purpose of this study was to determine how commensal bacteria alter the host response to sepsis. Conventional and germ free (GF) C57Bl/6 mice were subjected to Pseudomonas aeruginosa pneumonia. All GF mice died within two days while 44% of conventional mice survived for 7 days (p=0.001). Diluting the dose of bacteria 10-fold in GF mice led to similar survival in GF and conventional mice. When animals with similar mortality were assayed for intestinal integrity, GF mice had lower levels of intestinal epithelial apoptosis but similar levels of proliferation and intestinal permeability. GF mice had significantly lower levels of TNF and IL-1β in BAL fluid compared to conventional mice without changes in systemic cytokine production. Under conventional conditions, sepsis unmasks lymphocyte control of intestinal epithelial apoptosis, since sepsis induces a greater increase in gut apoptosis in Rag-1−/− mice than wild type (WT) mice. However, in a separate set of experiments, gut apoptosis was similar between septic GF Rag-1−/− mice and septic GF WT mice. These data demonstrate that the endogenous bacteria play a protective role in mediating mortality from pneumonia-induced sepsis, potentially mediated through altered intestinal apoptosis and the local pro-inflammatory response. Additionally, sepsis-induced lymphocyte-dependent increases in gut epithelial apoptosis appear to be mediated by the endogenous bacteria.