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  

Genistein antagonizes paraoxon-induced high expressions of NADPH oxidase p22phox and Nox4 in rat thoracic aorta tissues

作　　者：刘玉玲[1,2] 汪煜华[1] 张秀芹[1] 李冬花[1] 黄红林[1] 

机构地区：[1]湖南省高等学校药物蛋白质组学重点实验室南华大学药物药理研究所,湖南衡阳421001 [2]娄底市卫生学校,湖南娄底417000

出　　处：《中国药理学通报》2015年第9期1292-1298,共7页Chinese Pharmacological Bulletin

基　　金：湖南省十二五重点学科建设项目;湖南省中医药管理局重点项目资助(No 201314)

摘　　要：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。Aim To investigate whether genistein protects paraoxon-induced vascular endothelial dysfunction through down-regulating p22 phox 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 aortas 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 of40. 5 μmol · L- 1for 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 p22 phox and Nox4 mRNA were detected by RT-PCR and the protein expressions of p 2 2 phox and Nox 4 were detectedby Western blot. Results Compared with the control group,the expressions of p22 phox and Nox4 were markedly increased in the paraoxon group. In the genistein group,the expressions of p22 phox 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 significant difference in the expression of p22 phox. The expression of p22 phox in the paraoxon plus genisteingroup was significantly decreased（ P〈0. 05） as compared 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 p22 phox and Nox4 expressions,genistein may down-regulate the expressions of both and protect vascular endothelium.

关 键 词：染料木素 对氧磷 氧化性损伤 NADPH氧化酶 P22PHOX NOX4 

分 类 号：R-322[医药卫生] R322.121