From the Adelaide Medical School and Robinson Research Institute, The University of Adelaide, Australia.
Hypertension. 2020 Jun;75(6):1363-1381. doi: 10.1161/HYPERTENSIONAHA.119.14598. Epub 2020 Apr 6.
Preeclampsia is a common pregnancy complication, affecting 2% to 8% of pregnancies worldwide, and is an important cause of both maternal and fetal morbidity and mortality. Importantly, although aspirin and calcium are able to prevent preeclampsia in some women, there is no cure apart from delivery of the placenta and fetus, often necessitating iatrogenic preterm birth. Preclinical models of preeclampsia are widely used to investigate the causes and consequences of preeclampsia and to evaluate safety and efficacy of potential preventative and therapeutic interventions. In this review, we provide a summary of the published preclinical models of preeclampsia that meet human diagnostic criteria, including the development of maternal hypertension, together with new-onset proteinuria, maternal organ dysfunction, and uteroplacental dysfunction. We then discuss evidence from preclinical models for multiple causal factors of preeclampsia, including those implicated in early-onset and late-onset preeclampsia. Next, we discuss the impact of exposure to a preeclampsia-like environment for later maternal and progeny health. The presence of long-term impairment, particularly cardiovascular outcomes, in mothers and progeny after an experimentally induced preeclampsia-like pregnancy, implies that later onset or reduced severity of preeclampsia will improve later maternal and progeny health. Finally, we summarize published intervention studies in preclinical models and identify gaps in knowledge that we consider should be targets for future research.
子痫前期是一种常见的妊娠并发症，影响全球 2%至 8%的妊娠，是孕产妇和胎儿发病率和死亡率的重要原因。重要的是，尽管阿司匹林和钙能够预防某些女性的子痫前期，但除了分娩胎盘和胎儿外，别无他法，这通常需要人为早产。子痫前期的临床前模型被广泛用于研究子痫前期的原因和后果，并评估潜在预防和治疗干预措施的安全性和有效性。在这篇综述中，我们总结了符合人类诊断标准的子痫前期临床前模型，包括母体高血压的发展，以及新出现的蛋白尿、母体器官功能障碍和胎盘功能障碍。然后，我们讨论了临床前模型中子痫前期多种病因的证据，包括与早发型和晚发型子痫前期有关的病因。接下来，我们讨论了暴露于类似子痫前期的环境对后期母婴健康的影响。在实验性诱导的类似子痫前期妊娠后，母亲和后代存在长期损害，特别是心血管结局，这意味着以后发病或严重程度降低的子痫前期将改善后期母婴健康。最后，我们总结了临床前模型中发表的干预研究，并确定了我们认为应该是未来研究目标的知识空白。
