Brooks H F, Osabutey C K, Moss R F, Andrews P L R, Davies D C
Division of Basic Medical Sciences and Image Resource Facility, St George's University of London, Cranmer Terrace, Tooting, London, UK.
Metab Brain Dis. 2007 Dec;22(3-4):353-73. doi: 10.1007/s11011-007-9058-1.
Sepsis is a major clinical challenge that is associated with encephalopathy and multi-organ dysfunction. Current therapeutic interventions are relatively ineffective and the development of novel treatments is hampered by the lack of a well-characterised animal model. Therefore, the behavioural, metabolic, physiological and histological changes resulting from 'through and through' caecal ligation and puncture (CLP) in the rat were investigated to determine its suitability as an animal model of human sepsis. CLP resulted in bacteraemia, characterised by the presence of multiple enteric species within 18-20 h. Locomotor activity was reduced within 4 h of CLP and this reduction increased with time. Pyrexia was evident 4-5 h after CLP and was followed by hypothermia beginning 17 h after intervention. CLP resulted in reduced white blood cell and platelet counts and an increased neutrophil: lymphocyte ratio within 18-20 h. It also resulted in decreased blood glucose, but not lactate levels. CLP caused histopathological changes in the cerebral cortex, liver, lungs and vascular system indicative of multi-organ dysfunction. Therefore, CLP in the rat mimics the cardinal clinical features of human sepsis and the subsequent development of multi-organ dysfunction. It appears to be the best available animal model currently available, in which to investigate the underlying pathophysiology of sepsis and identify therapeutic targets.
脓毒症是一项重大的临床挑战，与脑病和多器官功能障碍相关。目前的治疗干预措施相对无效，且由于缺乏特征明确的动物模型，新型治疗方法的研发受到阻碍。因此，研究了大鼠“全层”盲肠结扎和穿刺（CLP）所导致的行为、代谢、生理和组织学变化，以确定其作为人类脓毒症动物模型的适用性。CLP导致菌血症，其特征是在18 - 20小时内出现多种肠道菌种。CLP后4小时内运动活动减少，且这种减少随时间增加。CLP后4 - 5小时出现发热，随后在干预后17小时开始出现体温过低。CLP导致白细胞和血小板计数减少，中性粒细胞与淋巴细胞比例在18 - 20小时内增加。它还导致血糖降低，但乳酸水平未降低。CLP引起大脑皮层、肝脏、肺和血管系统的组织病理学变化，表明存在多器官功能障碍。因此，大鼠的CLP模拟了人类脓毒症的主要临床特征以及随后多器官功能障碍的发展。它似乎是目前可用于研究脓毒症潜在病理生理学和确定治疗靶点的最佳动物模型。
