Protective effect of metformin on the NG-nitro-l-arginine methyl ester (l-NAME)-induced rat models of preeclampsia

Abstract

Background

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.