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探讨

Investigation of 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)、肿瘤坏死因子α(TNF-α)含量的变化。结果rBPI21治疗1组(rBPI21剂量为0.625mg/kg)大鼠,6,12h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TNF-α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1.25,2.5,5.0mg/kg)大鼠各检测时间点血浆LPS、血清TNF-α含量均明显降低(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,减少TNF-α等细胞因子的过度表达。

Objective To investigate the protective mechanism of recombinant bactericidal permeability-increasing protein 21 （rBPI 21 ） in rat endotoxemia. Methods Different doses of rBPI 21 were injected in endotoxemia rats and the changes of lipopolysaccharide （LPS） and tumor necrosis factor-α（TNF-α） in blood of all groups were continuously observed. Results 6 and 12 hours after the injection,the levels of LPS in group 1 with rBPI 21 treatment （0.625 mg/kg） were significantly lower than those in endotoxin group at the same time. Serum TNF- α in group 1 with rBPI 21 treatment were lower than those in endotoxin group at any time point （P 〈 0.01 ）. Compared with the endotoxin group,the levels of LPS and TNF-α in groups 2,3 and 4 with rBPI 21 treatment （1.25 mg/kg,2.5 mg/kg,5.0 mg/kg,respectively） markedly dropped at any time points（P 〈 0.01 ）. Conclusion The protection of rBPI 21 in endotoxemia rots is primarily achieved through neutralizing LPS , decreasing LPS reaction in vivo and inhibiting TNF-α synthesis.