Roberts J M
Magee Womens Research Institute, Pittsburgh, PA 15213-3180, USA.
Semin Reprod Endocrinol. 1998;16(1):5-15. doi: 10.1055/s-2007-1016248.
Several years ago the hypothesis was advanced that alterations of endothelial function could explain much of the pathophysiology of preeclampsia. Since that time, extensive data have been generated to support the hypothesis. Markers of endothelial activation can be demonstrated in women with overt preeclampsia. More importantly, many of these markers precede clinically evident disease and disappear with resolution of the disease. The original postulate was that materials produced by the poorly perfused placenta, which is characteristic of preeclampsia, entered the systemic circulation and altered endothelial cell activity. This was proposed to change vascular sensitivity to circulating pressors, activate coagulation, and reduce vascular integrity resulting in the pathophysiological changes of preeclampsia. As data have accumulated it has become increasingly evident that the insult to the endothelium is neither toxicity nor nonspecific injury but rather can better be characterized as endothelial activation. Candidate molecules have been suggested but not established. It seems likely that the responsible agent(s) will not be unique molecules but rather usual molecules present in excessive amounts. The hypothesis has been expanded to invoke involvement of the maternal constitution in the generation of endothelial injury and injurants. This concept is stimulated by the observation that reduced placental perfusion per se is not sufficient to generate the maternal syndrome. Women with growth-restricted fetuses frequently are not preeclamptic. Placental bed biopsies from not only growth-restricted but also prematurely born infants demonstrate failure of the physiological remodeling of decidual vessels responsible for the reduced placental perfusion of preeclampsia. This has led to the concept that preeclampsia is secondary to an interaction of reduced placental perfusion and maternal factors. Interestingly these maternal factors, obesity, insulin resistance, black race, hypertension, and elevated plasma homocysteine concentration are all risk factors for atherosclerosis in later life.
几年前，有人提出假说，认为内皮功能改变可以解释先兆子痫的大部分病理生理学机制。自那时起，已产生了大量数据来支持这一假说。在显性先兆子痫女性中可检测到内皮激活标志物。更重要的是，许多此类标志物在临床明显疾病出现之前就已存在，并随着疾病的缓解而消失。最初的假设是，先兆子痫所特有的胎盘灌注不良产生的物质进入体循环并改变内皮细胞活性。这被认为会改变血管对循环加压物质的敏感性，激活凝血，并降低血管完整性，从而导致先兆子痫的病理生理变化。随着数据的积累，越来越明显的是，对内皮的损伤既不是毒性作用也不是非特异性损伤，而更确切地可被描述为内皮激活。已提出了一些候选分子，但尚未确定。似乎致病因子不太可能是独特的分子，而更可能是过量存在的常见分子。该假说已扩展到认为母体体质参与了内皮损伤和损伤因子的产生。这一概念受到以下观察结果的启发，即胎盘灌注减少本身不足以引发母体综合征。胎儿生长受限的女性通常不会患先兆子痫。不仅是生长受限胎儿，早产婴儿的胎盘床活检也显示，负责先兆子痫胎盘灌注减少的蜕膜血管生理性重塑失败。这导致了一种概念，即先兆子痫是胎盘灌注减少与母体因素相互作用的结果。有趣的是，这些母体因素，肥胖、胰岛素抵抗、黑人种族、高血压和血浆同型半胱氨酸浓度升高，都是日后发生动脉粥样硬化的危险因素。
