Genistein antagonizes paraoxon-induced high expressions of NADPH oxidase p22phox and Nox4 in rat thoracic aorta tissues / 中国药理学通报

ABSTRACT

Aim To investigate whether genistein pro-tects paraoxon-induced vascular endothelial dysfunction through down-regulating p22phox and Nox4 expressions as well as inhibiting the generation of ROS.Methods In this study,thoracic aortas were isolated from the male Sprague-Dawley(SD)rats and were divided into the following groups① control group,the thoracic a-ortas were incubated with dimethyl sulfoxide (DMSO, 0.1%)for 30 min;② genistein group,the thoracic a-ortas were incubated with genistein(100 μmol·L -1 ) for 30 min;③ paraoxon group,the thoracic aortas were incubated with paraoxon at the concentration of 40.5 μmol · L -1 for 30 min; ④ paraoxon plus genistein groups,the thoracic aortas were incubated with paraoxon (40.5 μmol·L -1 )plus genistein (100μmol·L -1 )for 30 min.The expressions of p22phox and Nox4 mRNA were detected by RT-PCR and the protein expressions ofp 2 2 phox and Nox4 were detected by Western blot.Results Compared with the control group,the expressions of p22phox and Nox4 were markedly increased in the paraoxon group. In the genistein group,the expressions of p22phox and Nox4 were significantly repressed. When treated with genistein plus paraoxon,there was a marked increase in the expression of Nox4(P <0.05),but no signifi-cant difference in the expression of p22phox.The ex-pression of p22phox in the paraoxon plus genistein group was significantly decreased(P <0.05)as com-pared with paraoxin group,but there was no significant difference in the expression of Nox4.Conclusion Paraoxon may result in oxidative damage of vascular endothelium through up-regulating p22phox and Nox4 expressions,genistein may down-regulate the expres-sions of both and protect vascular endothelium.