Animal models of sepsis.
Animal models of sepsis.
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DOI：
10.4161/viru.26083
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发表时间：
2014-01-01
期刊：
影响因子：
5.2
通讯作者：
Fink MP
中科院分区：
文献类型：
--
作者：
Fink MP
脓毒症仍然是一种常见、严重且异质性的临床实体，很难充分定义。尽管脓毒症作为一个公共卫生问题很重要，但开发用于脓毒症辅助治疗的特定治疗剂并获得监管部门批准的努力却非常不成功。开发辅助治疗脓毒症的新药物的关键途径之一是在人类状况的适当动物模型中进行评估。不幸的是，用于此目的的动物模型经常产生误导性的结果。脓毒症动物模型药理学试验结果与人体临床试验结果之间的差异可能有多种原因。重要原因之一可能是由创伤或感染引发的基因表达变化在临床前测试常用物种小鼠和人类中是不同的。此外，包括小鼠和狒狒在内的许多物种对细菌脂多糖的毒性作用具有显着的抵抗力，而人类则极其敏感。正在研究使用动物进行败血症研究的新方法。但目前，必须以一定程度的怀疑态度看待脓毒症新治疗药物的临床前研究结果。
Sepsis remains a common, serious, and heterogeneous clinical entity that is difficult to define adequately. Despite its importance as a public health problem, efforts to develop and gain regulatory approval for a specific therapeutic agent for the adjuvant treatment of sepsis have been remarkably unsuccessful. One step in the critical pathway for the development of a new agent for adjuvant treatment of sepsis is evaluation in an appropriate animal model of the human condition. Unfortunately, the animal models that have been used for this purpose have often yielded misleading findings. It is likely that there are multiple reasons for the discrepancies between the results obtained in tests of pharmacological agents in animal models of sepsis and the outcomes of human clinical trials. One of important reason may be that the changes in gene expression, which are triggered by trauma or infection, are different in mice, a commonly used species for preclinical testing, and humans. Additionally, many species, including mice and baboons, are remarkably resistant to the toxic effects of bacterial lipopolysaccharide, whereas humans are exquisitely sensitive. New approaches toward the use of animals for sepsis research are being investigated. But, at present, results from preclinical studies of new therapeutic agents for sepsis must be viewed with a degree of skepticism.
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