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富氢盐水调节脓毒症小鼠肠道屏障功能障碍、菌群失调和细菌易位。

Hydrogen-Rich Saline Regulates Intestinal Barrier Dysfunction, Dysbiosis, and Bacterial Translocation in a Murine Model of Sepsis.

机构信息

Department of Traumatology and Acute Critical Medicine, Osaka University Graduate School of Medicine, Osaka, Japan.

Department of Microbiology and Immunology, Osaka University Graduate School of Medicine, Osaka, Japan.

出版信息

Shock. 2018 Dec;50(6):640-647. doi: 10.1097/SHK.0000000000001098.

Abstract

Bacterial translocation is a major cause of multiple organ dysfunction syndrome in critical illness, and its management is an important therapeutic strategy. In this study, we focused on the key factors responsible for bacterial translocation including the intestinal microbiome and investigated the impact of molecular hydrogen therapy as a countermeasure against bacterial translocation in a murine model of sepsis. The experimental protocols were divided into the sham, saline treatment (control), and hydrogen treatment (H2) groups. In the H2 group, 15 mL/kg of hydrogen-rich saline (7 ppm) was gavaged daily for 7 days following cecal ligation and puncture (CLP). In the control group, normal saline was gavaged in the same way. In the results, the 7-day survival rate was significantly improved in the H2 group versus the control group (69% vs. 31%, P < 0.05). The incidence of bacterial translocation at 24 h after CLP as assessed by cultivation of mesenteric lymph nodes and blood was significantly decreased in the H2 group versus the control group. Administration of hydrogen-rich saline also prevented the expansion of facultative anaerobic Enterobacteriaceae and ameliorated intestinal hyperpermeability at 24 h after CLP. Intestinal tissue levels of inflammatory mediators such as inducible nitric oxide synthases, tumor necrosis factor α, interleukin (IL)-1β, IL-6, and oxidative stress marker malondialdehyde at 6 h after CLP were down-regulated in the H2 group. These results suggest luminal administration of hydrogen-rich saline, which prevents intestinal dysbiosis, hyperpermeability, and bacterial translocation, could potentially be a new therapeutic strategy in critical illness.

摘要

细菌易位是危重病中多器官功能障碍综合征的主要原因,其治疗管理是一种重要的治疗策略。在这项研究中,我们专注于导致细菌易位的关键因素,包括肠道微生物组,并研究了分子氢治疗作为对抗脓毒症小鼠模型中细菌易位的对策的影响。实验方案分为假手术、盐水治疗(对照)和氢气治疗(H2)组。在 H2 组中,在盲肠结扎和穿刺(CLP)后每天通过灌胃给予 15 mL/kg 的富氢盐水(7 ppm),持续 7 天。在对照组中,以相同的方式灌胃生理盐水。结果显示,与对照组相比,H2 组的 7 天生存率显著提高(69%比 31%,P<0.05)。通过肠系膜淋巴结和血液培养评估 CLP 后 24 小时的细菌易位发生率,H2 组明显低于对照组。富氢盐水的给药还防止了兼性厌氧菌肠杆菌科的扩张,并改善了 CLP 后 24 小时的肠道高通透性。CLP 后 6 小时,H2 组肠道组织中诱导型一氧化氮合酶、肿瘤坏死因子 α、白细胞介素(IL)-1β、IL-6 和氧化应激标志物丙二醛等炎症介质的水平下调。这些结果表明,腔内给予富氢盐水可以防止肠道菌群失调、通透性增加和细菌易位,可能成为危重病的一种新的治疗策略。

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