Cardiovascular-Renal Research Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS.
Cardiovascular-Renal Research Center, Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, MS.
Am J Obstet Gynecol. 2022 Feb;226(2S):S973-S987. doi: 10.1016/j.ajog.2020.10.025. Epub 2021 Mar 12.
Animal models have been critical in investigating the pathogenesis, mediators, and even therapeutic options for a number of diseases, including preeclampsia. Preeclampsia is the leading cause of maternal and fetal morbidity and mortality worldwide. The placenta is thought to play a central role in the pathogenesis of this disease because it releases antiangiogenic and proinflammatory factors into the maternal circulation, resulting in the maternal syndrome. Despite the deleterious effects preeclampsia has been shown to have on the mother and baby during pregnancy and postpartum, there is still no effective treatment for this disease. Although clinical studies in patients are crucial to identify the involvement of pathogenic factors in preeclampsia, there are obvious limitations that prevent detailed investigation of the quantitative importance of time-dependent mechanisms involved in this syndrome. Animal models allow investigators to perform proof-of-concept studies and examine whether certain factors found in women with preeclampsia mediate hypertension and other manifestations of this disease. In this brief review, we summarize some of the more widely studied models used to investigate pathophysiological mechanisms that are thought to be involved in preeclampsia. These include models of placental ischemia, angiogenic imbalance, and maternal immune activation. Infusion of preeclampsia-related factors into animals has been widely studied to understand the specific mediators of this disease. These models have been included, in addition to a number of genetic models involved in overexpression of the renin-angiotensin system, complement activation, and trophoblast differentiation. Together, these models cover multiple mechanisms of preeclampsia from trophoblast dysfunction and impaired placental vascularization to the excess circulating placental factors and clinical manifestation of this disease. Most animal studies have been performed in rats and mice; however, we have also incorporated nonhuman primate models in this review. Preclinical animal models not only have been instrumental in understanding the pathophysiology of preeclampsia but also continue to be important tools in the search for novel therapeutic options for the treatment of this disease.
动物模型在研究许多疾病的发病机制、介质甚至治疗选择方面发挥了关键作用，包括子痫前期。子痫前期是全球孕产妇和胎儿发病率和死亡率的主要原因。胎盘被认为在这种疾病的发病机制中起着核心作用，因为它将抗血管生成和促炎因子释放到母体循环中，导致母体综合征。尽管子痫前期已被证明会在妊娠和产后对母亲和婴儿造成有害影响，但目前仍没有针对这种疾病的有效治疗方法。尽管对患者进行临床研究对于确定致病因素在子痫前期中的参与至关重要，但仍存在明显的局限性，无法详细研究与该综合征相关的时间依赖性机制的定量重要性。动物模型允许研究人员进行概念验证研究，并检查在患有子痫前期的女性中发现的某些因素是否介导高血压和这种疾病的其他表现。在这篇简短的综述中，我们总结了一些更广泛研究的模型，用于研究被认为与子痫前期有关的病理生理机制。这些模型包括胎盘缺血、血管生成失衡和母体免疫激活模型。将与子痫前期相关的因子输注到动物中已被广泛研究，以了解这种疾病的特定介质。除了涉及肾素-血管紧张素系统、补体激活和滋养层分化的过度表达的许多遗传模型外，这些模型也包括在内。这些模型涵盖了子痫前期的多种机制，从滋养层功能障碍和胎盘血管化受损到循环胎盘因子过多和这种疾病的临床表现。大多数动物研究都是在大鼠和小鼠中进行的；然而，我们在这篇综述中也纳入了非人类灵长类动物模型。临床前动物模型不仅有助于理解子痫前期的病理生理学，而且在寻找治疗这种疾病的新治疗选择方面也继续是重要工具。
