Department of Obstetrics, First Clinical College of Shanxi Medical University, Taiyuan, Shanxi Province, PR China.
Department of Obstetrics, First Clinical College of Shanxi Medical University, Taiyuan, Shanxi Province, PR China.
Biochem Biophys Res Commun. 2024 Dec 20;739:150996. doi: 10.1016/j.bbrc.2024.150996. Epub 2024 Nov 13.
Preeclampsia (PE) is a complex multi-organ disorder characterized by systemic inflammation, endothelial dysfunction, and vasoconstriction, which manifests as hypertension, with or without proteinuria. Effective preventive strategies for PE are currently lacking in clinical practice, leading to significant morbidity and mortality among mothers and newborns.
This study aims to investigate the impact of metformin (MET) on the l-NAME-induced PE rat model, focusing on the mechanisms through which MET may exert its effects.
Thirty pregnant Sprague-Dawley (SD) rats were randomly assigned to three groups: Control, PE, and PE + MET, on gestational day 0 (GD0). Regularly measure blood pressure and 24-h proteinuria, and collect tissue samples on GD20. Enzyme-linked immunosorbent assay (ELISA) was used to analyze inflammatory factors, endothelial function biomarkers, angiogenic factors, and apoptosis-related factors in the rat plasma. Western blot, RT-qPCR, and immunohistochemistry techniques were employed to determine the expression levels of key apoptotic proteins in placental tissue.
The study findings demonstrate that MET administration improves blood pressure and 24-h proteinuria, alleviates fetal growth restriction, ameliorate inflammation cytokines, and restores the balance of angiogenic factors and endothelial function. Moreover, MET inhibits the expression levels of critical apoptotic proteins in the plasma and placental tissue of PE-like rats.
The results suggest that MET shows promise in alleviating symptoms associated with l-NAME-induced PE in rats, preserving endothelial function, enhancing angiogenesis, reducing inflammation, inhibiting placental apoptosis, improving placental function, and promoting fetal growth. These findings highlight MET as a potential therapeutic agent for the prevention and treatment of preeclampsia.
子痫前期（PE）是一种复杂的多器官功能障碍，其特征是全身炎症、内皮功能障碍和血管收缩，表现为高血压，伴有或不伴有蛋白尿。目前临床上缺乏有效的预防策略，导致母亲和新生儿发病率和死亡率显著增加。
本研究旨在探讨二甲双胍（MET）对 l-NAME 诱导的 PE 大鼠模型的影响，重点研究 MET 发挥作用的机制。
30 只妊娠 Sprague-Dawley（SD）大鼠随机分为 3 组：对照组、PE 组和 PE+MET 组，于妊娠第 0 天（GD0）开始。定期测量血压和 24 小时尿蛋白，并于 GD20 收集组织样本。采用酶联免疫吸附试验（ELISA）检测大鼠血浆中炎症因子、内皮功能生物标志物、血管生成因子和凋亡相关因子。采用 Western blot、RT-qPCR 和免疫组织化学技术检测胎盘组织中关键凋亡蛋白的表达水平。
研究结果表明，MET 给药可改善血压和 24 小时尿蛋白，减轻胎儿生长受限，改善炎症细胞因子，恢复血管生成因子和内皮功能平衡。此外，MET 抑制 PE 样大鼠血浆和胎盘组织中关键凋亡蛋白的表达水平。
结果表明，MET 可缓解 l-NAME 诱导的 PE 大鼠的症状，保护内皮功能，增强血管生成，减轻炎症，抑制胎盘细胞凋亡，改善胎盘功能，促进胎儿生长。这些发现表明 MET 可能是预防和治疗子痫前期的一种潜在治疗药物。
