Faculty of Environmental Science and Engineering, Kunming University of Science and Technology, Kunming, 650500, China.
Medical School, Kunming University of Science and Technology, Kunming, 650500, China.
Fundam Clin Pharmacol. 2019 Dec;33(6):649-658. doi: 10.1111/fcp.12501. Epub 2019 Aug 13.
Recent in vitro and clinical studies have found that metformin (MET) may play a preventive or therapeutic role in preeclampsia (PE) and may be a candidate drug for the prevention and/or treatment of PE. In this study, we used lipopolysaccharide (LPS) to induce a PE-like rat model and investigated the intervention effect of MET from the perspectives of clinical manifestations, placental morphology, serum marker for placental injury, systemic inflammatory response and oxidative/nitrative stress, and placental nuclear factor-κB (NF-κB) signaling. The results showed that MET improved LPS-induced hypertension, proteinuria, fetal growth restriction (FGR) and stillbirth, alleviated placental injury and decreased maternal serum marker alpha-fetoprotein (MS-AFP) level; MET suppressed LPS-induced TNF-α and IL-6 productions, reduced oxidative/nitrative stress as evidenced by increased superoxide dismutase (SOD) activity, decreased inducible nitric oxide synthase (iNOS) activity, and decreased levels of malondialdehyde (MDA) and nitric oxide (NO); MET inhibited LPS-induced NF-κB activation in placentas. Based on these findings, it can be concluded that MET is beneficial to the PE-like rat model by protecting placentas from injury, suppressing systemic inflammatory response and oxidative/nitrative stress, and inhibiting placental NF-κB signaling pathway. MET is a promising drug for prevention and/or treatment of PE.
最近的体外和临床研究发现二甲双胍（MET）可能在子痫前期（PE）中发挥预防或治疗作用，并且可能是预防和/或治疗 PE 的候选药物。在这项研究中，我们使用脂多糖（LPS）诱导 PE 样大鼠模型，从临床表现、胎盘形态、胎盘损伤血清标志物、全身炎症反应和氧化/硝化应激以及胎盘核因子-κB（NF-κB）信号通路的角度研究了 MET 的干预作用。结果表明，MET 改善了 LPS 诱导的高血压、蛋白尿、胎儿生长受限（FGR）和死胎，减轻了胎盘损伤并降低了母血清标志物甲胎蛋白（MS-AFP）水平；MET 抑制了 LPS 诱导的 TNF-α 和 IL-6 的产生，减少了氧化/硝化应激，表现为超氧化物歧化酶（SOD）活性增加，诱导型一氧化氮合酶（iNOS）活性降低，丙二醛（MDA）和一氧化氮（NO）水平降低；MET 抑制了 LPS 诱导的胎盘 NF-κB 激活。基于这些发现，可以得出结论，MET 通过保护胎盘免受损伤、抑制全身炎症反应和氧化/硝化应激以及抑制胎盘 NF-κB 信号通路，有益于 PE 样大鼠模型。MET 是预防和/或治疗 PE 的有前途的药物。
