Dexmedetomidine improves mitophagy and pyroptosis through the ALKBH5/FUNDC1 axis during epidural-related maternal fever

Epidural analgesia has emerged as a commonly used method for relieving labor pain. However, epidural-related maternal fever (ERMF) is characterized by a high occurrence rate and can have detrimental consequences for the well-being of both the mother and the fetus. This study aimed to investigate the functional role and underlying mechanism of dexmedetomidine (DEX) in ERMF. Ropivacaine (ROP)-induced human umbilical vein endothelial cells (HUVECs) were treated with DEX and/or transfected with ALKBH5 or FUNDC1 overexpression plasmid. qPCR and Western blot were adopted for mitophagy and pyroptosis marker protein detection. Autophagosomes were observed through electron microscopy, Caspase-1/PI double-positive cells were determined using flow cytometry. Inflammation-related factors were quantified using ELISA. The N6-methyladenosine (m6A) modification of FUNDC1 mRNA was examined using methylated RNA immunoprecipitation (MeRIP) and the binding between ALKBH5 and FUNDC1 mRNA was confirmed by RNA immunoprecipitation (RIP). In ROP-induced HUVECs, there was a significant upregulation in ALKBH5 and FUNDC1, resulting in a notable increase in inflammation, pyroptosis, and mitophagy. The administration of DEX demonstrated the ability to alleviate ROP-induced pyroptosis and promote protective mitophagy. Interestingly, DEX treatment significantly reduced the interaction between ALKBH5 and FUNDC1 mRNA, while simultaneously increasing the m6A level of FUNDC1 mRNA in ROP-treated cells. Moreover, the overexpression of FUNDC1 partially reversed the effects of ALKBH5 overexpression on mitophagy and pyroptosis in HUVECs. DEX can promote mitophagy and inhibit pyroptosis through the ALKBH5/FUNDC1 axis in ERMF, indicating its potential as a therapeutic strategy for clinical ERMF treatment.