糖皮质激素对内毒素耐受的影响

目的应用地塞米松(dexamethasone,Dex)干预小鼠内毒素耐受的形成,研究糖皮质激素对内毒素耐受的影响。方法以昆明鼠为实验对象进行分组,ⅠA组为健康对照组,ⅠB组为单次直接致死剂量脂多糖(lipopolysaccharide,LPS)(2LD50=8 mg/kg)对照组,Ⅱ组为标准内毒素耐受组,ⅢA组为初始LPS刺激前高剂量Dex(10 mg/kg)干预组,ⅢB组为终末致死量LPS前高剂量Dex干预组,ⅣA组为初始LPS刺激前低剂量Dex(1mg/kg)干预组,ⅣB组为终末致死量LPS前低剂量Dex干预组。完成实验处置后3 h取血标本,应用ELISA方法检测血清TNF-α和IL-10水平。结果①ⅠA组TNF-α、IL-10水平极低,ⅠB组TNF-α、IL-10水平较ⅠA组显著增高(P<0.05,P<0.01),Ⅱ组TNF-α、IL-10水平较ⅠB组显著下降(P<0.05,P<0.01),但仍高于ⅠA组。②各Dex干预组TNF-α水平与Ⅱ组比较:ⅢA、ⅣA组TNF-α水平与Ⅱ组TNF-α水平差异无统计学意义(P>0.05),ⅢB、ⅣB组TNF-α水平低于Ⅱ组,差异有统计学意义(P<0.05)。③各Dex干预组IL-10水平与Ⅱ组比较:ⅢA、ⅣA组IL-10水平高于Ⅱ组,差异有统计学意义(P<0.05),ⅢB、ⅣB组IL-10水平与Ⅱ组比较差异无统计学意义(P>0.05)。结论①LPS刺激可导致小鼠体内TNF-α水平、IL-10水平升高。内毒素耐受时,小鼠体内TNF-α、IL-10水平升高的程度明显降低。②终末LPS前一定时间内予以Dex干预可以促进内毒素耐受的形成,Dex剂量过高可能不会带来更多受益。③IL-10对内毒素耐受的形成可能不具有决定作用。

Effect of glucocorticoid on endotoxin tolerance

Objective To investigate the effects of glucocorticoid on endotoxin tolerance,the formation of endotoxin tolerance in mice was intervened by using dexamethasone（ Dex）. Methods Kunming mice as experimental objects were divided into seven groups. GroupⅠA for healthy control,groupⅠB for once lethal dose lipopolysaccharide（ LPS）（ 2LD50 =8 mg/kg） control,groupⅡfor classical endotoxin tolerance,groupⅢA for pretreated high dose Dex（ 10 mg/kg） before initial LPS stimulation,groupⅢB for pretreated high dose Dex before terminal lethal dose of LPS intervention,groupⅣA for pretreated low dose Dex（ 1 mg /kg） before initial LPS stimulation,groupⅣB for pretreated low dose Dex before terminal lethal dose of LPS intervention. 3 hours after experimental management,blood specimen was obtained. Enzyme-linked immunosorbent assay was used to detect serum tumour necrosis factor-α（ TNF-α）,and interleukin-10（ IL-10） levels. Results TNF-α and IL-10 levels of groupⅠA were extremely low,and TNF-α and IL-10 levels of groupⅠB were significantly higher（ P〈0. 05,P〈0. 01）. TNF-α and IL-10 levels of group Ⅱ compared with that of group Ⅰ B dropped significantly（ P〈0. 05,P〈0. 01）,but which were still higher than that of groupⅠA. The comparison of TNF-αlevels of the Dex intervention groups with that of groupⅡ： TNF-α levels of groupⅢA and groupⅣA had no significant difference（ P〉 0. 05）. TNF-α levels of groupⅢB and groupⅣB were lower（ P〈0. 05）. The comparison of IL-10 levels of the Dex intervention groups with that of groupⅡ： IL-10 levels of groupⅢA and groupⅣA were higher（ P〈0. 05）. IL-10 levels of groupⅢB and groupⅣB had no significant differentce（ P 〉0. 05）. Conclusion 1. LPS stimulation could elevate TNF-α and IL-10 levels in mice. When mice developed endotoxin tolerance,their elevated levels of TNF-α and IL-10 decreased obviously. 2. Within a certain duration before terminal LPS intervention,pretreatment with Dex could pr