Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Department of Emergency Medicine, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA.
Int J Mol Sci. 2023 May 31;24(11):9578. doi: 10.3390/ijms24119578.
In the development of therapeutic strategies for human diseases, preclinical experimental models have a key role. However, the preclinical immunomodulatory therapies developed using rodent sepsis were not successful in human clinical trials. Sepsis is characterized by a dysregulated inflammation and redox imbalance triggered by infection. Human sepsis is simulated in experimental models using methods that trigger inflammation or infection in the host animals, most often mice or rats. It remains unknown whether the characteristics of the host species, the methods used to induce sepsis, or the molecular processes focused upon need to be revisited in the development of treatment methods that will succeed in human clinical trials. Our goal in this review is to provide a survey of existing experimental models of sepsis, including the use of humanized mice and dirty mice, and to show how these models reflect the clinical course of sepsis. We will discuss the strengths and limitations of these models and present recent advances in this subject area. We maintain that rodent models continue to have an irreplaceable role in studies toward discovering treatment methods for human sepsis.
在人类疾病治疗策略的发展中，临床前实验模型起着关键作用。然而，使用啮齿动物脓毒症开发的临床前免疫调节疗法在人类临床试验中并未取得成功。脓毒症的特征是由感染引发的炎症失调和氧化还原失衡。使用在宿主动物（通常是小鼠或大鼠）中引发炎症或感染的方法来模拟人类脓毒症。目前尚不清楚在开发将在人类临床试验中取得成功的治疗方法时，是否需要重新审视宿主物种的特征、用于诱导脓毒症的方法或关注的分子过程。我们在这篇综述中的目标是提供对现有的脓毒症实验模型的调查，包括使用人源化小鼠和脏鼠，并展示这些模型如何反映脓毒症的临床过程。我们将讨论这些模型的优缺点，并介绍该领域的最新进展。我们认为，啮齿动物模型在发现人类脓毒症治疗方法的研究中仍然具有不可替代的作用。
