高壓氧氣治療內毒素誘發小鼠全身性發炎反應症候群模式的療效及細胞素影響與對肝臟保護效果之研究

Abstract

高壓氧治療可以提高組織內氧氣濃度並改善敗血症中低血壓和代謝性酸中毒的情形，而且高壓氧治療還可以對於免疫系統在不同情況下產生抑制或加強的效果。本實驗設計以腹腔內注射內毒素(lipopolysaccharide, LPS)12.5mg/kg誘發小鼠產生全身性發炎反應症候群(systemic inflammatory response syndrome , SIRS)之後，給予即時的高壓氧治療(2ATA,75分鐘)來評估高壓氧治療於內毒素誘發小鼠全身性發炎反應症候群的情形下對其存活率的影響與效果，並且佐以其對細胞素的抑制或促進效果來推究其可能之作用機轉。此外，多重器官衰竭是敗血病最終死亡的重要原因，而肝臟衰竭又為其最重要之指標。所以本實驗也同時觀察高壓氧治療對於內毒素誘發小鼠全身性發炎反應症候群時肝臟的保護效果。實驗結果如下：一、於注射內毒素後即刻給予高壓氧治療(2ATA,75分鐘)可以將內毒素誘發小鼠全身性發炎反應症候群的死亡率由75%下降到25%，而且可以明顯降低腫瘤壞死因子(tumor necrosis factor-α,TNF-α)的濃度，同時也相對的可以明顯提高介白素-10(Interleukin-10, IL-10)的濃度；另外也有保護肝臟免於急性大量壞死的作用。以上結果顯示，早期即時的高壓氧治療對於內毒素誘發小鼠全身性發炎反應症候群具有療效，同時可保護肝臟免於急性衰竭。其效果可能來自於高壓氧氣降低與調節發炎反應的調控。

The present study is designed to reveal the possible mechanism and the therapeutic potential for hyperbaric oxygen therapy (HBO) in the treatment of sepsis , also protection effect on liver during sepsis. Immediate HBO treatment ( 2 ATA , 75 min ) was applied to assess the survival rate of septic BALB/c mice induced by LPS within 84 hours period. The changes of plasma TNF-α and IL-10 after LPS challenge were measured. The pathological change of liver at 24 hours after LPS challenge treated with/without HBO treatment were also studied. The experimental results demonstrates that: (1) immediate HBO exposure after LPS challenge increases the survival rate of mice from 25% to 75%, (2) the plasma concentration of TNF-α after LPS challenge is reduced by immediate HBO treatment, (3) HBO treatment may protect liver from septic injury. In conclusion , HBO treatment exerts beneficial effects on sepsis induced by LPS in BALB/c mouse. The possible mechanism may be due to immunomodulation effect of HBO on immune system.