Propofol upregulates MFG‑E8 in BV2 cells to inhibit pyroptosis mediated by the NF‑κB/NLRP3 pathway, thereby ameliorating ischemic‑reperfusion neuronal injury

Abnormal activation and pyroptosis of microglia caused by cerebral ischemia‑reperfusion injury (CIRI) are key mechanisms underlying neuronal damage. The NF‑κB/NLRP3 pathway is a core mediator of microglial pyroptosis and neuroinflammatory cascades in CIRI. Milk fat globule‑EGF factor 8 (MFG‑E8) is a critical anti‑inflammatory and neuroprotective factor. Propofol (PPF) exhibits antioxidant activity and ameliorates neuronal injury, but its effects on CIRI and underlying mechanisms remain unclear. The present study aimed to investigate whether PPF alleviates neuronal injury by modulating NF‑κB/NLRP3 pathway via regulating MFG‑E8 expression. An oxygen‑glucose deprivation/reoxygenation (OGD/R) model was established using mouse microglial BV‑2 and hippocampal neuronal HT22 cells and cell survival was assessed via Cell Counting Kit‑8 assay. Polarity in BV‑2 cells was evaluated using flow cytometry, while cell death was assessed by Calcein AM/PI and TUNEL staining. A transient middle cerebral artery occlusion (tMCAO) mouse model was established and neurological deficit scores were assessed. The impacts of PPF on cortical damage, neuroinflammation, apoptosis and pyroptosis in tMCAO mice were observed by histopathological staining. Inflammatory factor levels were assessed using ELISA kits. Western blotting was performed to assess MFG‑E8, pyroptosis and NF‑κB/NLRP3 pathway‑related proteins. OGD/R decreased viability, increased apoptosis and pyroptosis rates in BV‑2 and HT22 cells and promoted M1 polarization in BV‑2 cells; PPF treatment reversed these effects. MFG‑E8 was downregulated in OGD/R‑treated BV2 cells, while PPF upregulated MFG‑E8 expression. Additionally, PPF decreased cerebral infarction volume in tMCAO mice, improved neurological deficit score, mitigated pathological brain tissue damage and decreased the number of degenerating neurons. PPF also inhibited pro‑inflammatory microglia activation and decreased pro‑inflammatory factor levels. Mechanistically, PPF suppressed NF‑κB pathway activation and downregulated NLRP3 by upregulating MFG‑E8; silencing MFG‑E8 reduced the protective effects of PPF in tMCAO mice and OGD/R cell models. PPF improved neuronal injury in CIRI by upregulating MFG‑E8 to inhibit pyroptosis induced by the NF‑κB/NLRP3 pathway.