Department of Gynecology and Obstetrics, the First Hospital of Shanxi Medical University (First Clinical Medicine College), Taiyuan City, Shanxi Province 030001, China.
Department of Gynecology and Obstetrics, the First Hospital of Shanxi Medical University (First Clinical Medicine College), Taiyuan City, Shanxi Province 030001, China.
Gene. 2024 Aug 15;919:148509. doi: 10.1016/j.gene.2024.148509. Epub 2024 Apr 25.
It is widely acknowledged that Metformin (MET), an established medication for managing type 2 diabetes, possesses diverse pharmacological effects. This study aims to investigate the protective effects of MET against Nω-Nitro-L-arginine methyl ester (L-NAME)-induced preeclampsia (PE).
Sprague Dawley (SD) rats were exposed to 200 mg/kg L-NAME with or without prior MET treatment. Histopathological analysis was performed using Hematoxylin and Eosin staining. Serum levels of inflammatory, antiangiogenic, and angiogenic factors were quantified using ELISA kits. Immunohistochemistry (IHC) staining was employed to observe NLRP3 and IL-1β expressions in placental tissues. Western blot and Quantitative Real-Time PCR (q-PCR) analyses were conducted to assess protein and mRNA expressions of NLRP3, caspase-1, ASC, and IL-1β.
We found that MET could mitigate placental histopathological deterioration and improve pregnancy outcomes in L-NAME-induced PE rat models. MET not only suppressed L-NAME-induced elevation of antiangiogenic factors but also stimulated the production of pro-angiogenic factors. Additionally, MET treatment reversed the excessive inflammatory response induced by L-NAME. Furthermore, MET inhibited the activation of the NLRP3 inflammasome triggered by L-NAME, evidenced by the downregulation of NLRP3 expression, caspase-1, and IL-1β.
MET demonstrates a protective effect against L-NAME-induced PE rats, potentially mediated through inhibition of the inflammatory response, downregulation of NLRP3 inflammasome expression in the placenta, and regulation of the balance between anti-angiogenic and pro-angiogenic factors.
众所周知，二甲双胍（MET）是一种用于治疗 2 型糖尿病的既定药物，具有多种药理作用。本研究旨在探讨 MET 对 Nω-硝基-L-精氨酸甲酯（L-NAME）诱导的先兆子痫（PE）的保护作用。
用或不用 MET 预先处理，SD 大鼠暴露于 200mg/kg L-NAME。用苏木精和伊红染色进行组织病理学分析。用 ELISA 试剂盒定量测定血清中炎症、抗血管生成和血管生成因子的水平。用免疫组化（IHC）染色观察胎盘组织中 NLRP3 和 IL-1β的表达。用 Western blot 和定量实时 PCR（q-PCR）分析评估 NLRP3、caspase-1、ASC 和 IL-1β的蛋白和 mRNA 表达。
我们发现 MET 可减轻 L-NAME 诱导的 PE 大鼠模型中胎盘组织学恶化并改善妊娠结局。MET 不仅抑制了 L-NAME 诱导的抗血管生成因子的升高，还刺激了促血管生成因子的产生。此外，MET 逆转了 L-NAME 诱导的过度炎症反应。此外，MET 抑制了由 L-NAME 触发的 NLRP3 炎性小体的激活，证据是 NLRP3 表达、caspase-1 和 IL-1β下调。
MET 对 L-NAME 诱导的 PE 大鼠具有保护作用，可能通过抑制炎症反应、下调胎盘 NLRP3 炎性小体表达以及调节抗血管生成和促血管生成因子之间的平衡来介导。
