Abstract:

Objective To observe the effect of propofol on endothelial nitric oxide synthase (eNOS) activation, and explore the regulation role of protein kinase C-ε (PKC-ε) in drug-induced eNOS activation in human umbilical vein endothelial cells (HUVECs) model. Methods HUVECs of the third to fifth passages cultured in vitro were selected. Cells were treated with propofol (0 μmol/L, 1 μmol/L, 5 μmol/L, 10 μmol/L, 50 μmol/L and 100 μmol/L) for 1 h and 24 h respectively, and the concentration-effect relationship of propofol in activation of eNOS was analysed. Cells were exposed to propofol (5 μmol/L and 50 μmol/L) for 0 min, 5 min, 1 h, 6 h and 24 h, and time-effect relationship of propofol in activation of eNOS was explored. Then, cultured HUVECs were randomly divided into normal control group, PKC-ε pseudosubstrate+ propofol 5 μmol/L group, PKC-ε pseudosubstrate+ propofol 50 μmol/L group, single PKC-ε pseudosubstrate group, single propofol 50 μmol/L group and 10% long chain fat emulsion group. Cells in each group were treated for 1 h and 24 h respectively. The expression of PKC-ε, eNOS and P-Ser1177-eNOS protein was detected by Western blotting. Results Propofol increased the expression of P-Ser1177-eNOS protein in concentration- and time-dependent manners. When cells were treated for 24 h, the expression of P-Ser1177-eNOS protein in PKC-ε pseudosubstrate+ propofol 50 μmol/L group was significantly lower than that in single propofol 50 μmol/L group （P＜0.05). Conclusion Propofol induces the activation of eNOS in concentration- and time-dependent manners, and PKC-ε positively mediates the activation of eNOS induced by propofol.

Key words: propofol, endothelial nitric oxide synthase, protein kinase C-ε, human umbilical vein endothelial cell