Volatile
anesthetics modulate endothelial cell apoptosis and inhibit nuclear factor-κB (NF-κB) signaling. In this study, we aimed to assess whether
desflurane preconditioning protects human umbilical vein endothelial cells (HUVECs) agaist
anoxia/reoxygenation (A/R) injury. HUVECs were pre-conditioned with
desflurane (1.0 MAC) for 30 min, followed by a 15-min washout, then exposed to 60 min
anoxia and 60 min reoxygenation (A/R), and incubated with 10 ng/ml
tumor necrosis factor (TNF)-α for 60 min. HUVEC viability and apoptosis were measured by MTT assay and
annexin V staining, and immunoblot analysis was used to measure the levels of Smac and cellular inhibitor of apoptosis 1 (cIAP1). NF-κB activation was assessed using the NF-κB signaling pathway real‑time PCR array, and the levels of NF-κB inducing
kinase (NIK), p52, IκB
kinase (IKK)α, p100, RelB and NLR family, pyrin domain containing 12 (NLRP12) were assessed by immunoblot analysis.
Desflurane preconditioning attenuated the effects of A/R and/or A/R plus TNF-α on cell viability, decreasing the levels of Smac and enhancing the levels of of cIAP1 (P<0.05). Preconditioning with
desflurane also enhanced the
mRNA levels of
interleukin (IL)-10 and NLRP12 in the cells exposed to A/R by 2.40- and 2.16‑fold, respectively. The HUVECs exposed to A/R had greater levels of NIK and p100 and reduced levels of p52 and IKKα. Desflurance preconditioning further increased p100 levels, decreased the level of NIK, further decreased p52 levels and further reduced IKKα levels. A/R in combination with TNF-α increased the NIK, IKKα, p100 and RelB levels, and this increase was significantly attenuated by desflurance preconditioning (all P<0.05).
Desflurane preconditioning enhanced HUVEC survival and protected the cells against A/R injury, and our results suggested that this process involved the upregulation of NLRP12 and the inhibition of non-canonical NF-κB signaling.