Abstract

Postoperative cognitive dysfunction is a common complication following anesthesia and surgery, and is associated with oxidative stress and apoptosis in the central nervous system. Resveratrol, an antioxidant, natural polyphenol, has been reported to have neuroprotective effect. The aim of this study was to examine whether resveratrol could attenuate the apoptosis and oxidative stress in a cell model of postoperative cognitive dysfunction. A cell model of postoperative cognitive dysfunction was constructed using human microglial clone 3 cells exposed to 1000 ng/ml lipopolysaccharide, 50 µM resveratrol, and their combination for 48 h. Then, the cell viability, proliferation, apoptosis, production of reactive oxygen species, and the expression of apoptosis-related genes and nuclear factor-E2-related factor 2 and its downstream antioxidant genes were examined. In the postoperative cognitive dysfunction cell model, lipopolysaccharide decreased the cell viability and proliferation, while it increased cell apoptosis and reactive oxygen species level. Lipopolysaccharide also upregulated the expression of pro-apoptotic genes (Bcl-2-associated X-protein and caspase-3) and genes involved in nuclear factor-E2-related factor 2-mediated antioxidant pathway (nuclear factor-E2-related factor 2, Kelch-like ECH-associated protein 1, heme oxygenase-1, and superoxide dismutase-2) in human microglial clone 3 cells. Resveratrol ameliorated the lipopolysaccharide-induced decrease of cell viability and proliferation, increase of cell apoptosis and reactive oxygen species level, and upregulation of the expression of pro-apoptotic genes. Additionally, resveratrol upregulated the expression of nuclear factor-E2-related factor 2 and its downstream antioxidant genes in lipopolysaccharide-treated human microglial clone 3 cells. Resveratrol protects human microglial clone 3 cells against lipopolysaccharide-induced injury by reducing oxidative stress through activating nuclear factor-E2-related factor 2-mediated antioxidant pathway.