染料木素拮抗对氧磷诱导的大鼠胸主动脉组织 p22phox 表达上调

摘要

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 groups:① 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.%目的：探讨染料木素是否通过下调 p22phox、Nox4的表达，抑制活性氧的生成而拮抗对氧磷损伤的血管内皮功能。方法取♂ SD 大鼠胸主动脉。①溶媒对照组：用0.1％的二甲基亚砜（dimethyl sulfoxide，DMSO）处理大鼠胸主动脉30 min；②染料木素（genistein，GST）处理组：GST （100μmol · L －1）处理大鼠胸主动脉30 min；③对氧磷（paraoxon，PO）处理组：PO（40.5μmol·L －1）处理大鼠胸主动脉30 min；④ PO ＋GST 处理组：PO（40.5μmol·L －1）＋GST（100μmol·L －1）处理大鼠胸主动脉30 min。RT-PCR法检测各组 p22phox、Nox4 mRNA 表达的变化；Western blot观察 p22phox 和 Nox4蛋白表达的变化。结果较之溶媒对照组，PO 处理可使 p22phox、Nox4 mRNA 及蛋白表达明显增加；GST 处理则使 p22phox、Nox4 mRNA 及蛋白表达明显减少；PO ＋GST 共同处理组，Nox4 mRNA 及蛋白表达增加。与PO 单独处理组比较，PO ＋GST 共同处理组 p22phox mRNA及蛋白表达明显减少。结论对氧磷可通过上调血管组织p22phox、Nox4 mRNA 和蛋白的表达，导致血管内皮氧化损伤；染料木素可下调二者的表达，保护血管内皮。