Buras Jon A, Holt Douglas, Orlow Daniel, Belikoff Bryan, Pavlides Stavros, Reenstra Wende R
New England Inflammation and Tissue Protection Institute Consortium at Northeastern University, Boston, MA, USA.
Crit Care Med. 2006 Oct;34(10):2624-9. doi: 10.1097/01.CCM.0000239438.22758.E0.
This study was performed to determine whether hyperbaric oxygen (HBO2) therapy is protective in cecal ligation and puncture (CLP)-induced sepsis and if protection is dependent on oxygen dosing. We also wished to determine whether HBO2 affected bacterial clearance or altered macrophage production of interleukin-10 (IL-10)s in the setting of CLP sepsis. Finally, we wished to determine whether the mechanism of HBO2 protection in sepsis was dependent on IL-10 production.
Prospective, experimental study.
University experimental research laboratory.
C57BL/6 and C57BL/6 IL-10 mice.
Sepsis was induced by CLP. Mice were randomized to receive a 1.5-hr HBO2 treatment at either 1, 2.5, or 3 atmospheres absolute every 12 hrs or HBO2 at 2.5 atmospheres absolute every 24 hrs. Mice were also harvested at 24 hrs for determination of bacterial load and isolation and study of CD11b peritoneal macrophages.
Survival was monitored for 100 hrs after CLP +/- HBO2 treatment. HBO2 significantly improved survival when administered at 2.5 atmospheres absolute every 12 hrs. Other treatment schedules were not protective, and treatment at 3.0 atmospheres absolute significantly worsened survival outcome. Bacterial load was significantly reduced in splenic homogenates but not peritoneal fluid at 24 hrs. Macrophages isolated from HBO2-treated mice demonstrated enhanced IL-10 secretion in response to lipopolysaccharide as compared with CLP controls. Mice genetically deficient in IL-10 expression treated with HBO2 at 2.5 atmospheres absolute every 12 hrs were not protected from CLP-induced mortality.
HBO2 may be protective in CLP sepsis within a window of oxygen dosing. The mechanism of HBO2 protection may be potentially linked in part to expression of IL-10, as peritoneal macrophages demonstrated enhanced IL-10 expression and IL-10 mice were not protected by HBO2 treatment.
本研究旨在确定高压氧（HBO₂）治疗对盲肠结扎穿刺（CLP）诱导的脓毒症是否具有保护作用，以及这种保护作用是否依赖于氧剂量。我们还希望确定HBO₂在CLP脓毒症情况下是否影响细菌清除或改变巨噬细胞白细胞介素-10（IL-10）的产生。最后，我们希望确定HBO₂在脓毒症中的保护机制是否依赖于IL-10的产生。
前瞻性实验研究。
大学实验研究实验室。
C57BL/6和C57BL/6 IL-10基因敲除小鼠。
通过CLP诱导脓毒症。小鼠被随机分为每12小时接受1.5小时1、2.5或3个绝对大气压的HBO₂治疗组，或每24小时接受2.5个绝对大气压的HBO₂治疗组。在24小时时也对小鼠进行取材，以测定细菌载量，并分离和研究CD11b腹腔巨噬细胞。
在CLP ± HBO₂治疗后监测100小时的生存率。每12小时给予2.5个绝对大气压的HBO₂治疗时，生存率显著提高。其他治疗方案无保护作用，3.0个绝对大气压的治疗显著恶化生存结局。24小时时脾匀浆中的细菌载量显著降低，但腹腔液中未降低。与CLP对照组相比，从接受HBO₂治疗的小鼠分离出的巨噬细胞对脂多糖刺激的反应显示出IL-10分泌增强。每12小时接受2.5个绝对大气压的HBO₂治疗的IL-10基因表达缺陷小鼠未免受CLP诱导的死亡。
在一定的氧剂量范围内，HBO₂可能对CLP脓毒症具有保护作用。HBO₂保护机制可能部分与IL-10的表达有关，因为腹腔巨噬细胞显示出IL-10表达增强，而IL-10基因敲除小鼠未受到HBO₂治疗的保护。
