Department of Molecular and Medical Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Department of Anesthesiology and Pain Relief Center, The University of Tokyo Hospital, Tokyo 113-8655, Japan.
Eur J Pharmacol. 2018 Aug 15;833:403-410. doi: 10.1016/j.ejphar.2018.06.031. Epub 2018 Jun 20.
Despite advances in overall medical care, sepsis and its sequelae continue to be an embarrassing clinical entity with an unacceptably high mortality rate. The central reason for high morbidity and high mortality of sepsis and its sequelae is the lack of an effective treatment. Previous clinical trials have largely failed to identify an effective therapeutic target to improve clinical outcomes in sepsis. Thus, the key goal favoring the outcome of septic patients is to devise innovative and evolutionary therapeutic strategies. Gene therapy can be considered as one of the most promising novel therapeutic approaches for nasty disorders. Since a number of transcription factors, such as nuclear factor-κB (NF-κB) and activator protein-1 (AP-1), play a pivotal role in the pathophysiology of sepsis that can be characterized by the induction of multiple genes and their products, sepsis may be regarded as a gene-related disorder and gene therapy may be considered a promising novel therapeutic approach for treatment of sepsis. In this review article, we provide an up-to-date summary of the gene-targeting approaches, which have been developed in animal models of sepsis. Our review sheds light on the molecular basis of sepsis pathology for the development of novel gene therapy approaches and leads to the conclusion that future research efforts may fully take into account gene therapy for the treatment of sepsis.
尽管整体医疗水平有所提高,但脓毒症及其后遗症仍然是一个令人尴尬的临床实体,其死亡率高得令人无法接受。脓毒症及其后遗症发病率和死亡率高的核心原因是缺乏有效的治疗方法。以前的临床试验在很大程度上未能确定有效的治疗靶点,以改善脓毒症的临床结局。因此,有利于脓毒症患者结局的关键目标是设计创新和进化的治疗策略。基因治疗可以被认为是治疗棘手疾病最有前途的新治疗方法之一。由于许多转录因子,如核因子-κB(NF-κB)和激活蛋白-1(AP-1),在脓毒症的病理生理学中发挥着关键作用,它们可以诱导多种基因及其产物的表达,因此脓毒症可以被视为一种与基因相关的疾病,基因治疗可以被认为是治疗脓毒症的一种有前途的新治疗方法。在这篇综述文章中,我们提供了脓毒症动物模型中已经开发的基因靶向方法的最新总结。我们的综述揭示了脓毒症病理学的分子基础,为新型基因治疗方法的发展提供了依据,并得出结论,未来的研究工作可能会充分考虑基因治疗来治疗脓毒症。