Abstract
Introduction:
Preeclampsia (PE) is a pregnancy complication that leads to hypertension and proteinuria and causes maternal mortality. Metformin (MET) is an oral hypoglycemic agent that activates AMPK-regulated signaling pathways and inhibits inflammation and oxidative stress responses. This study explored MET's roles and molecular mechanisms in PE.
Methods:
The protein or mRNA expression of signaling pathways and inflammation-related genes were detected by Western blotting and RT-qPCR and cell viability was analyzed with MTT. In addition, flow cytometry was used to assess apoptosis, and mitochondrial membrane potential was detected using JC-1 staining with flow cytometry. Moreover, LDH Cytotoxicity Assay Kit detected the release of LDH, and ROS, MDA, or SOD kits detected oxidative stress-related factors.
Results:
MET significantly inhibited inflammatory damage and oxidative stress responses in LPS-induced HTR-8/SVneo cells. Besides, MET could activate AMPK and then affect NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways in LPS-induced HTR-8/SVneo cells. Compound C (an AMPK inhibitor) significantly reversed MET's effects on LPS-stimulated HTR-8/SVneo cells.
Discussion:
MET attenuated inflammatory and oxidative stress of HTR-8/SVneo cells in PE by activating AMPK to regulate NF-κB/sFlt-1 and Nrf2/HO-1 signaling pathways, suggesting that MET was a potential therapeutic drug for PE.
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