Barichello Tatiana, Machado Roberta Albino, Constantino Larissa, Valvassori Samira S, Réus Gislaine Z, Martins Marcio Rodrigo, Petronilho Fabricia, Ritter Cristiane, Quevedo João, Dal-Pizzol Felipe
Laboratório de Fisiopatologia Experimental, Universidade do Extremo Sul Catarinense, Criciúma, Santa Catarina, Brazil.
Crit Care Med. 2007 Sep;35(9):2186-90. doi: 10.1097/01.ccm.0000281452.60683.96.
Assess the effect of antioxidant treatment on late memory impairment and early hippocampus oxidative stress after cecal ligation and perforation.
Male Wistar rats.
Rats underwent sham operation or cecal ligation and perforation. Animals that underwent cecal ligation and perforation were divided into groups: 1) treated with basic support (50 mL/kg saline, 30 mg/kg ceftriaxone, and 25 mg/kg clindamycin every 6 hrs), 2) treated with basic support plus N-acetylcysteine (20 mg/kg N-acetylcysteine at 3, 6, 12, 18, and 24 hrs after cecal ligation and perforation), 3) treated with basic support plus deferoxamine (20 mg/kg deferoxamine at 3 and 24 hrs after cecal ligation and perforation), 4) treated with basic support plus N-acetylcysteine and deferoxamine, or 5) treated with N-acetylcysteine plus deferoxamine.
On days 10 and 30 after surgery, the animals underwent behavioral tasks: inhibitory avoidance task, habituation to an open field, and continuous multiple-trials step-down inhibitory avoidance task. The sepsis group showed significantly decreased performance in latency retention compared with the sham group in the inhibitory avoidance task. In the open-field task, the sepsis group presented memory impairment after sepsis. In the continuous multiple-trials step-down inhibitory avoidance task, the sepsis group showed a significant increase in the number of training trials required to reach the acquisition criterion. All these memory impairments were prevented by N-acetylcysteine plus deferoxamine treatment, but not its isolate use. In addition, the combined use of antioxidants attenuated oxidative damage in hippocampus 6 hrs after sepsis induction.
Antioxidant treatment prevented the development of late cognitive deficits in an animal model of sepsis.
评估抗氧化治疗对盲肠结扎穿孔术后晚期记忆障碍及早期海马氧化应激的影响。
雄性Wistar大鼠。
大鼠接受假手术或盲肠结扎穿孔手术。接受盲肠结扎穿孔手术的动物被分为以下几组：1）接受基础支持治疗（每6小时给予50 mL/kg生理盐水、30 mg/kg头孢曲松和25 mg/kg克林霉素）；2）接受基础支持治疗加N-乙酰半胱氨酸（在盲肠结扎穿孔后3、6、12、18和24小时给予20 mg/kg N-乙酰半胱氨酸）；3）接受基础支持治疗加去铁胺（在盲肠结扎穿孔后3小时和24小时给予20 mg/kg去铁胺）；4）接受基础支持治疗加N-乙酰半胱氨酸和去铁胺；或5）接受N-乙酰半胱氨酸加去铁胺治疗。
在术后第10天和第30天，动物接受行为测试：抑制性回避任务、旷场适应及连续多次递减式抑制性回避任务。脓毒症组在抑制性回避任务中的潜伏期保留表现与假手术组相比显著降低。在旷场任务中，脓毒症组在脓毒症后出现记忆障碍。在连续多次递减式抑制性回避任务中，脓毒症组达到习得标准所需的训练次数显著增加。所有这些记忆障碍均被N-乙酰半胱氨酸加去铁胺治疗所预防，但单独使用其中一种则无此效果。此外，抗氧化剂联合使用可减轻脓毒症诱导后6小时海马的氧化损伤。
抗氧化治疗可预防脓毒症动物模型中晚期认知缺陷的发生。
