抗生素诱导革兰阴性杆菌释放内毒素的实验研究(二)

An experimental study of the LPS release from gram-negative bacteria induced by antibiotics (Part two)

目的 探讨 β 内酰胺类抗生素在诱导革兰阴性菌释放内毒素 (LPS)及对感染动物保护效能方面的差异。 方法 制备大鼠烫伤创面脓毒症模型。将大鼠随机分为单纯抗生素治疗组 ,半乳糖胺 (GalN)敏化后治疗组及爱兰苔胶 (CGN)封闭后治疗组。分别用亚胺培南 (IMP ,5mg)和头孢他啶 (CTZ ,10mg)单剂量腹腔注射治疗 ,对照组施以同量无菌等渗盐水 ,敏化组加用GalN 5 0mg ,封闭组在敏化组的基础上加用CGN 1mg。于抗生素治疗后不同时相点检测血中细菌浓度、血浆LPS水平 ,观察敏化组和封闭组大鼠 10d后的死亡率。 结果 IMP和CTZ均能显著降低大鼠血中细菌量 ;IMP和CTZ在杀菌过程中能诱导PA10 3释放大量LPS ,但CTZ组血浆LPS水平显著超过相应的IMP组 (P<0 .0 5～ 0 .0 1) ;敏化组大鼠的死亡率CTZ组明显高于IMP组 (P <0 .0 5 ) ;封闭组两者间的差异消失(P>0 0 5 )。 结论 IMP和CTZ的杀菌效能无显著性差异 ,但在诱导细菌释放LPS的能力方面CTZ>IMP ;两者间的差异直接影响到对感染动物的各自保护作用 ,提示临床应用时 ,选择低诱导力的抗生素 (如IMP)可能更为合理。

Objective To explore the effects of di fferent β lactam antibiotics on the inducing of LPS release from gram negativ e bacteria and on the protection of infected animals. Methods Wistar rats were employed as the model and were inflicte d by 30% TBSA III degree scalding and sepsis caused by PA103. The rats were rand omly divided into 3 groups, i.e. simple antibiotic treatment group(A), treatment after sensitization with galactosamine (GalN) group (G) and treatment after blo cking with carrageenan (CGN) group (C). The rats were injected intra peritoneal ly with imipenem(IMP,5 mg) and ceftazidime(CTZ, 10mg) for single time, respectiv ely. Same amount of aseptic normal saline was injected in the control group, and GalN (50mg) was added in G and CGN (1mg) in C groups. The blood bacterial conce ntration and plasma LPS levels were determined at different time points after th e treatment by antibiotics. The mortality was observed in G and C groups at 10 d ays after treatment. Results The blood bacterial amount could be decreased by both IM P and CTZ evidently. Large amounts of LPS released from PA103 could be induced b y IMP and CTZ during their bactericidal process. But the plasma LPS level in rat s treated by CTZ was markedly higher than that by IMP (P<0.05～0.01). The mo r tality in G group treated by CTZ was much higher than that by IMP (P<0.05). Nevertheless, the mortality in C groups was the same no matter CTZ or IMP was ap plied (P<0.05) Conclusion There was no difference of the bactericidal power bet ween IMP and CTZ. But CTZ was more powerful in inducing LPS release from bacteri a than IMP. It was implied by the difference between these two antibiotics that IMP might be better choice in clinical application for burn infection due to its lower potential of inducing LPS release from the bacteria.