Ghiselli Roberto, Giacometti Andrea, Cirioni Oscar, Mocchegiani Federico, Orlando Fiorenza, D'Amato Giuseppina, Sisti Valerio, Scalise Giorgio, Saba Vittorio
Department of General Surgery, INRCA IRRCS, University of Ancona, Ancona, Italy.
Ann Surg. 2004 Feb;239(2):251-6. doi: 10.1097/01.sla.0000108673.25385.03.
To investigate the efficacy of imipenem, piperacillin combined with cecropin B in the prevention of lethality in 2 rat models of septic shock. Main outcome measures were bacterial growth in blood and intra-abdominal fluid, endotoxin and TNF-alpha concentrations in plasma, and lethality.
Sepsis remains a serious clinical problem despite intense efforts to improve survival. It is a major cause of morbidity and mortality in hospitalized patients. The primary cause of Gram-negative shock results from activation of host effector cells by endotoxin, the lipopolysaccharide (LPS) associated with cell membranes of Gram-negative bacteria.
Adult male Wistar rats were given (1). an intraperitoneal injection of 1 mg of Escherichia coli 0111:B4 LPS or (2). 2 x 1010 CFU of E. coli ATCC 25922. All animals were randomized to receive intraperitoneally isotonic sodium chloride solution, 1 mg/kg cecropin B, 20 mg/kg imipenem, and 120 mg/kg piperacillin alone and combined with 1 mg/kg cecropin B. Each group included 20 animals. RESULTS All compounds reduced the lethality when compared with controls. Piperacillin and imipenem significantly reduced the lethality and the number of E. coli in abdominal fluid compared with saline treatment. On the other hand, each betalactam determined an increase of plasma endotoxin and TNF-alpha concentration. Combination between cecropin B and betalactams showed to be the most effective treatment in reducing all variables measured.
Cecropin B enhances betalactams activities in Gram-negative sepic shock rat models.
研究亚胺培南、哌拉西林联合天蚕素B预防两种大鼠脓毒性休克致死率的效果。主要观察指标为血液和腹腔液中的细菌生长情况、血浆中内毒素和肿瘤坏死因子-α的浓度以及致死率。
尽管为提高生存率付出了巨大努力，但脓毒症仍然是一个严重的临床问题。它是住院患者发病和死亡的主要原因。革兰氏阴性菌休克的主要原因是内毒素（与革兰氏阴性菌细胞膜相关的脂多糖，LPS）激活宿主效应细胞。
成年雄性Wistar大鼠接受（1）腹腔注射1mg大肠杆菌0111:B4脂多糖或（2）2×10¹⁰CFU大肠杆菌ATCC 25922。所有动物随机分为腹腔注射等渗氯化钠溶液、1mg/kg天蚕素B、20mg/kg亚胺培南、120mg/kg哌拉西林组，以及上述药物与1mg/kg天蚕素B联合使用组。每组包括20只动物。结果与对照组相比，所有化合物均降低了致死率。与生理盐水治疗相比，哌拉西林和亚胺培南显著降低了致死率和腹腔液中大肠杆菌的数量。另一方面，每种β-内酰胺类药物都导致血浆内毒素和肿瘤坏死因子-α浓度升高。天蚕素B与β-内酰胺类药物联合使用在降低所有测量变量方面显示出最有效的治疗效果。
在革兰氏阴性脓毒性休克大鼠模型中，天蚕素B增强了β-内酰胺类药物的活性。
