Problotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis
Problotic bacteria prevent hepatic damage and maintain colonic barrier function in a mouse model of sepsis
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DOI：
10.1002/hep.21750
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发表时间：
2007-09-01
期刊：
影响因子：
13.5
通讯作者：
Madsen, Karen
中科院分区：
文献类型：
--
作者：
Ewaschuk, Julia;Endersby, Ryan;Madsen, Karen
肠道屏障功能的破坏和细菌移位的增加是脓毒症和肝脏疾病发病机制中的关键事件。用非侵入性和免疫调节性益生菌改变肠道菌群已被提出作为一种预防性治疗，以减少细菌移位的水平和预防脓毒症的发生。本研究的目的是确定益生菌化合物在减轻脓毒症小鼠模型中的肝和肠损伤中的功效。向野生型和白介素-10（IL-10）基因缺陷型129 Sv/Ev小鼠饲喂益生菌化合物VSL#3 7天。为了诱导脓毒症，在存在和不存在过氧化物酶体增殖物激活受体γ（PPAR γ）抑制剂GW 9662的情况下，向小鼠注射脂多糖（OLPS）和D-半乳糖胺（GaIN）。6小时后处死小鼠，取出其结肠用于测量细胞因子产生和上皮功能。用甘露醇测定功能性通透性。运动和环磷酸腺苷依赖性氯分泌的组织安装在尤辛室。分析肝脏的细菌移位、细胞因子产生、组织学损伤和PPAR γ水平。采用半定量逆转录聚合酶链反应测定肿瘤坏死因子α、干扰素γ、IL-6和IL-12 p35核糖核酸的组织水平。注射LPS/Ga 1 N的小鼠表现出结肠屏障功能的破坏，这与增强的促炎症细胞因子分泌、细菌易位和显著的肝损伤相关。口服益生菌预处理可防止肠道屏障功能的破坏，减少细菌移位，并显著减轻肝损伤。GW 9662对PPARgamma的抑制消除了益生菌诱导的保护作用。结论：口服益生菌通过PPAR γ依赖性机制预防脓毒症小鼠模型的肝脏和肠道损伤。
A breakdown in intestinal barrier function and increased bacterial translocation are key events in the pathogenesis of sepsis and liver disease. Altering gut microflora with noninvasive and immunomodulatory probiotic organisms has been proposed as an adjunctive therapy to reduce the level of bacterial translocation and prevent the onset of sepsis. The purpose of this study was to determine the efficacy of a probiotic compound in attenuating hepatic and intestinal injury in a mouse model of sepsis. Wild-type and interleukin-10 (IL-10) gene-deficient 129 Sv/Ev mice were fed the probiotic compound VSL#3 far 7 days. To induce sepsis, the mice were injected with lipopolysaccharide OLPS) and D-galactosamine (Ga1N in the presence and absence of the peroxisome proliferator-activated receptor gamma (PPAR gamma) inhibitor GW9662. The mice were killed after 6 hours, and their colons were removed for the measurement of the cytokine production and epithelial function. The functional permeability was assessed by the mannitol. movement and cyclic adenosine monophosphate- dependent chloride secretion in tissue mounted in Ussing chambers. The livers were analyzed for bacterial translocation, cytokine production, histological injury, and PPAR gamma levels. The tissue levels of tumor necrosis factor alpha, interferon gamma, IL-6, and IL-12p35 ribonudeic acid were measured by semiquantitative reverse transcription polymerase chain reaction. Mice injected with LPS/Ga1N demonstrated a breakdown in colonic barrier function, which correlated with enhanced proinflaminatory cytokine secretion, bacterial translocation, and significant hepatic injury. A pretreatment with oral probiotics prevented the breakdown in intestinal barrier function, reduced bacterial translocation, and significantly attenuated liver injury. The inhibition of PPAR gamma with GW9662 abrogated the protection induced by probiotics. Conclusion: Orally administered probiotics prevented liver and intestinal damage in a mouse model of sepsis through a PPAR gamma-dependent mechanism.