Desflurane preconditioning protects human umbilical vein endothelial cells against anoxia/reoxygenation by upregulating NLRP12 and inhibiting non-canonical nuclear factor-kappa B signaling

作者：Sun Zhirong; Lv Jianing; Zhu Yun; Song Dongli; Zhu Biao; Miao Changhong^*

来源：International Journal of Molecular Medicine, 2015, 36(5): 1327-1334.

DOI：10.3892/ijmm.2015.2335

• desflurane preconditioning
• NLRP12
• nuclear factor-kappa B
• human umbilical vein endothelial cells
• anoxia/reoxygenation

Volatile anesthetics modulate endothelial cell apoptosis and inhibit nuclear factor-kappa B (NF-kappa B) 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 preconditioned with desflurane (1.0 MAC) for 30 mm, followed by a 15-mM washout, then exposed to 60 mm anoxia and 60 mm reoxygenation (A/R), and incubated with 10 ng/ml tumor necrosis factor (TNF)-alpha 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-kappa B activation was assessed using the NF-kappa B signaling pathway real-time PCR array, and the levels of NF-kappa B inducing kinase (NIK), p52, I kappa B kinase (IKK)alpha, 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-alpha 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 IKK alpha. Desflurance preconditioning further increased p100 levels, decreased the level of NIK, further decreased p52 levels and further reduced IKK alpha levels. A/R in combination with TNF-alpha increased the NIK, IKK alpha, 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-kappa B signaling.

• 出版日期2015-11
• 单位复旦大学