DOI: 10.1002/ame2.70099
Revisiting the monocrotaline-treated rat as a model of inflammatory lung disease:COVID-19 and future pandemic threats?
Luke P.Kris1
Dani-Louise Dixon2
Shailesh Bihari2
Jillian M.Carr1
1.College of Medicine and Public Health,Flinders University,Adelaide,South Australia,Australia;Flinders Health and Medical Research Institute,Flinders University,Adelaide,South Australia,Australia2.College of Medicine and Public Health,Flinders University,Adelaide,South Australia,Australia;Flinders Health and Medical Research Institute,Flinders University,Adelaide,South Australia,Australia;ICU,Flinders Medical Centre,Adelaide,South Australia,Australia
摘要：The COVID-19 pandemic posed a challenge for clinical management of a new lung dis-ease that was characterized by inflammation,endothelial cell dysfunction,and throm-bosis,which occur after the replication phase of infection of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).There are many laboratory models of active SARS-CoV-2 infection in mice,reflecting an acute lung injury in an otherwise healthy animal,but there is a lack of accurate animal models of the postviral inflammatory phase of the COVID-19 lung reflecting severe disease.The monocrotaline(MCT)-treated rat is a widely used laboratory model of pulmonary hypertension(PH).Not often discussed,however,are the observed changes in inflammation,edema,fibrosis,and microthrom-bosis in the lung prior to PH.At the cellular level,there is loss of pneumocytes and endotheliopathy,and at the molecular level the MCT rat lung is characterized by a pro-inflammatory cytokine profile,namely elevated interleukin 6,transforming growth fac-tor β and tumor necrosis factor,M1 macrophage phenotype,and dysregulation of the angiotensin converting enzyme(ACE)/ACE2 balance.The systems-level pathophysiol-ogy of the MCT-treated rat includes progressive cardiopulmonary dysfunction.The MCT-treated rat clearly differs from the COVID-19 lung in terms of the triggers for pathology,but there are many parallels apparent in both the MCT-treated rat and the COVID-19 lung.The MCT-treated rat lung as a model of the COVID-19 lung may pro-vide an in-depth understanding of the factors that drive the lung to more severe pathol-ogy,treatments that benefit lung recovery,or the factors that prove a useful research platform for future emerging respiratory threats of similar pathology.
机标关键词：covid-19futuremodeldiseaseinflammatorylungmonocrotalinepandemic
论文发表日期：2025-10-30
在线出版日期：2025-12-16（本平台首次上网日期，不代表文献的发表时间）
页数：9( 1785-1793 )
英文信息