重组杀菌渗透性增加蛋白21在大鼠内毒素血症中保护机制的研究

Protective Mechanism of Recombinant Bactericidal Permeability-increasing Protein 21 in Rat Endotoxemia

目的探讨重组杀菌渗透性增加蛋白21(rBPI21)在大鼠内毒素血症中保护效应的机制。方法给内毒素血症大鼠注射不同剂量的rBPI21,动态观察rBPI21不同剂量组大鼠血液中内毒素(LPS)、脂多糖结合蛋白(LBP)、肿瘤坏死因子α(TNFα)含量的变化。结果rBPI21治疗1组(rBPI21剂量为0.625 mg/kg)大鼠,6、12 h血浆LPS含量明显低于内毒素组大鼠相同时间点LPS含量(P<0.01),血清LBP、TNFα含量各检测时间点均明显低于内毒素组大鼠相同时间点的含量(P<0.01);与内毒素组大鼠相比,rBPI21治疗2、3、4组(rBPI21剂量分别为1.25、2.5、5.0 mg/kg)大鼠各检测时间点血浆LPS,血清LBP、TNFα含量均明显降低,大鼠24 h生存率由内毒素组的16.7%分别上升到58.3%、91.7%、100.0%,差异有统计学意义(P<0.01)。结论rBPI21对内毒素血症大鼠的保护作用机制主要是通过促进体内LPS的聚合和清除,降低LPS活性,从而抑制LBP的生成,减少TNFα等细胞因子的过度表达。

OBJECTIVE To investigate the protective mechanism of recombinant bactericidal permeability-increasing protein 21 （rBPI21） in rat endotoxemia. METHODS The different dosage of rBPI21 in endotoxemia rats was injected and the changes in lipopolysaccharide（LPS）, lipopolysaccharide binding protein（LBP） and tumor necrosis factor a（TNFα） contents in blood of different group rats were continuously observed. RESULTS At 6 and 12 hours, the levels of LPS in rBPI21 treatment 1 group（rBPI21 dosage 0. 625 mg/kg） were significantly lower than those in endotoxin group at the same time. Serum LBP and TNFα in rBPI21 treatment 1 group were both lower than those in endotoxin group at any time point. Compared with the endotoxin group, the levels of LPS, LBP, and TNFα in rBPI21 treatment 2, 3 and 4 groups （rBPI21 dosage 1. 25 mg/kg, 2. 5mg/kg, and 5. 0mg/kg, respectively） markedly dropped at any time points, the survival rates were increased from 16. 7% （endotoxin group） to 58.3%, 91.7% and 100% （rBPI21 treatment 2,3, and 4 groups） individually. CONCLUSIONS The protection of rBPI21 in endotoxemia rats is primarily achieved through neutralizing LPS, decreasing LPS activity in vivo and inhibiting LBP and TNF-α synthesis. Key words：