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探讨β-内酰胺类抗生素在诱导革兰氏阴性菌释放内毒素 (L PS)及对感染动物保护效能方面的差异 ,旨在为临床上防治革兰氏阴性菌感染时正确选择抗生素提供实验依据。将 Wistar大鼠背部做 30 %TBSA( °)烫伤 ,创面立即涂铜绿假单胞菌 (PA10 3)悬液 1ml(1× 10 9CFU) ,72 h后制成大鼠烧伤创面脓毒症模型。烧伤脓毒症大鼠随机分为单纯抗生素治疗组、半乳糖胺 (Gal N)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,5 mg)和头孢他啶 (CTZ,10 mg)单剂量腹腔注射 (i.p.)治疗 ,对照组施以等量无菌生理盐水 ,同时 ,敏化组加用 Gal N 5 0 mg i.p.,以增强大鼠对 L PS的敏感性 ,封闭组在敏化组的基础上加用 CGN 1mg i.p.,以阻断 L PS的生物学效应。于抗生素治疗前及治疗后 3、6及 9h抽静脉血 ,检测血中细菌浓度 ,血浆 L PS水平 ,并观察敏化组和封闭组大鼠 10 d后的死亡率。结果 IMP和 CTZ均能使大鼠血中菌量显著降低 ;IMP和 CTZ在杀菌过程中均能诱导 PA10 3释放大量 L PS,但 CTZ组血浆 L PS水平显著超过相应的IMP组 (P<0 .0 5或 P<0 .0 1) ;与此同时 ,敏化组大鼠的死亡率 CTZ组明显高于 IMP组 (P<0 .0 5 ) ,而在封闭组 ,两者间的这种差异则消失 (P>0 .0 5 )。结果表明 ,同属β-内酰胺类的 IMP和 CTZ
To investigate the difference of β-lactam antibiotics in inducing L PS released by Gram-negative bacteria and the protective effect on animals infected with Gram-negative bacteria, so as to provide an experimental basis for the proper selection of antibiotics in the prevention and treatment of Gram-negative bacteria clinically . The Wistar rats were scalded with 30% TBSA (°) on their back. The wounds were immediately treated with 1 ml (1 × 10 9 CFU) suspension of Pseudomonas aeruginosa (PA10 3) and then made into a septic model of burn wound in rats. Burn sepsis rats were randomly divided into simple antibiotic treatment group, Gal N sensitized treatment group and achilles gum (CGN) closed treatment group. A single dose of imipenem (IMP, 5 mg) and ceftazidime (CTZ, 10 mg) were intraperitoneally injected (ip), and the control group was given sterile normal saline. Meanwhile, sensitized rats were treated with Gal N 5 0 mg ip, to enhance the sensitivity of rats to L PS, blocking group on the basis of the sensitized group with CGN 1mg ip, to block the biological effects of L PS. Venous blood was drawn before antibiotic treatment and at 3, 6, and 9 hours after treatment. Bacterial concentrations in blood and plasma LPS level were measured. Mortality after 10 days in sensitized and occluded groups was also observed. Results Both IMP and CTZ could significantly reduce the amount of bacteria in the blood of rats. Both IMP and CTZ induced a large release of L PS during the course of sterilization, but the level of L PS in CTZ group was significantly higher than that of the corresponding IMP group (P <0. .0 5 or P <0.01). In the meantime, the mortality of sensitized rats in CTZ group was significantly higher than that in IMP group (P <0.05), while in the blocking group, Variation disappeared (P> 0.05). The results showed that the same belong to the β-lactam IMP and CTZ