Maprotiline Attenuates Isoflurane-induced Microglial Inflammation

Background: Maprotiline intervention is noted to alleviate the body’s inflammatory response effectively, but its specific molecular mechanism remains elusive. Objectives: This study aimed to investigate the impact of maprotiline on the inflammatory response caused by isoflurane. Materials and Methods: Microglia BV-2 cells were grouped into control group, isoflurane group, maprotiline group, and positive control group, and were respectively receiving treatment of isoflurane (10 μg/mL) alone, isoflurane and maprotiline (10 μg/mL), and isoflurane and oxymethylene ketone (10 μmol/L), with cells of control group cultured alone. After treatments, the enzyme-linked immunosorbent assay (ELISA) assay detected BV-2 cell activity, BV-2 cell inflammatory response expression (interleukin 1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor (TNF)-α), ionized calcium-binding adapter molecule 1 (Iba-1) protein expression, toll-like receptor 4 (TLR4) protein, p-inhibitor of nuclear factor kappa B (p-IκBα) expression, nuclear P65, and cytoplasmic P65 expression. Results: The isoflurane group had the lowest BV-2 cell viability and the highest content of lactate dehydrogenase (LDH), followed by the maprotiline group and the positive control group (p < .05). As isoflurane induced the contents of IL-1β, IL-6, TNF-α, and Iba-1, the addition of maprotiline or oxymethylene ketone decreased the expressions of the inflammatory cytokines (p < .05) without significant difference between the maprotiline group and the positive control group (p > .05). The isoflurane group and the positive control group had the highest expression of TLR4 p-IκBα and nuclear P65 and the lowest expression of cytoplasmic P65, followed by the maprotiline group (p < .05). There was no significant difference between the isoflurane and positive control groups (p > .05). Conclusion: Maprotiline may enhance microglia activation and alleviate and reduce the isoflurane-induced inflammation of microglia through inhibition of TLR4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, P65 nuclear translocation, and IκBα phosphorylation.