Protective effects of propofol on lipopolysaccharide-activated endothelial cell barrier dysfunction

Abstract.

Background

Propofol has been widely used in intravenous anesthesia. It possesses antioxidant and immunomodulating effects. This study aimed to investigate whether propofol may attenuate lipopolysaccharide (LPS)-induced endothelial cell barrier dysfunction and the possible mechanisms of such modulation.

Methods

Cultured human umbilical vein endothelial cells (HUVECs) were used to assess the following treatments: (i) no additives (negative control), (ii) LPS alone (1 and 10 μg/ml), (iii) propofol alone (20 μg/ml), (iv) intralipid (a solvent of propofol) alone (20 μg/ml), (v) LPS (10 μg/ml) combination with propofol (4 and 20 μg/ml) and (vi) LPS (10 μg/ml) combination with intralipid (20 μg/ml). Changes of cell permeability and filamentous actin (F-actin) were determined. Expression of nitrotyrosine proteins and activity of nuclear factor κB (NF-κB) were analyzed by Western blot and immunocytochemistry. Expression of endothelial nitric-oxide synthase (eNOS) and inducible nitric-oxide synthase (iNOS) were analyzed by reverse transcriptase-polymerase chain reaction.

Results

LPS markedly increased the permeability of endothelial cells, the formation of peroxynitrite and depolymerization of F-actin in HUVECs. LPS also significantly increased mRNA of iNOS, protein level of NF-κB and decreased mRNA of eNOS (P  <  0.05). Propofol at both concentrations (4 and 20 μg/ml) significantly inhibited the LPS–induced increase in cell permeability and alteration in F-actin organization. Propofol also reduced the LPS-enhanced iNOS mRNA and NF-κB protein levels whilst it increased eNOS mRNA expression (P  <  0.05).

Conclusion

This study demonstrated that propofol, both at therapeutic concentrations and 5 times therapeutic concentrations, inhibited NF-κB activation in LPS-stimulated endothelial cells and was found to protect endothelial cells against LPS-induced barrier dysfunction.