NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响  

Role of NADPH oxidase in oxidative stress involved in spontaneously hypertensive rats

作　　者：郑建普[1] 孙莉[1] 可燕[1,2] 崔进[1] 朱春赟[1] 高月红[1] 卞卡[1,2,3] 

机构地区：[1]上海中医药大学穆拉德中药现代化研究中心 [2]上海高校一氧化氮与炎症医学E研究院,上海201203 [3]美国德克萨斯大学休斯顿医学院综合生物及药理学系·德克萨斯大学分子医学研究所,休斯顿TX77030

出　　处：《中国药理学通报》2006年第9期1079-1083,共5页Chinese Pharmacological Bulletin

基　　金：上海市教委高校一氧化氮与炎症医学E研究院计划资助项目(NoE-04010);上海市教委重点科研资助项目(No05ZZ11);上海市科委基础研究重点资助项目(No05JC14056)

摘　　要：目的考察NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响。方法22wk龄自发性高血压大鼠(SHR)和正常血压WKY大鼠,采用尾套法测定血压,Greiss反应测定血清一氧化氮分泌量,ABTS和FRAP法进行血清总抗氧化能力测定,血管环舒缩测定来评价超氧阴离子清除剂超氧化物歧化酶(SOD)和NADPH氧化酶抑制剂夹竹桃麻素(Apo)对大鼠腹主动脉内皮依赖性舒张反应;采用RT-PCR考察内皮型一氧化氮合酶(eNOS)、NADPH氧化酶亚基p22phox以及NADPH氧化酶亚基gp91phox类似物nox4mRNA表达。结果与WKY大鼠相比,SHR血压升高,而血清总抗氧化水平及NO分泌量均降低。PCR显示SHR胸主动脉中eNOS及p22phoxmRNA表达与WKY大鼠相比差异无显著性,而nox4表达则升高。SHR腹主动脉内皮依赖性舒张反应与WKY相比降低,SOD或Apo均能明显逆转该变化。结论结果提示SHR体内氧化应激状态与NADPH氧化酶gp91phox类似物nox4mRNA过表达有关;NADPH氧化酶依赖性的氧化应激参与了SHR内皮功能障碍的发生发展;药理调节NADPH氧化酶功能或应用抗氧化治疗可明显改善SHR内皮依赖性舒张反应。Aim This study was designed to investigate role of nicotinamide adenine dinucleotide phosphate oxidase （NADPH oxidase） in oxidative stress status of spontaneously hypertensive rats （SHR）. Methods Systolic blood pressure of 22 wk-old male SHR and age-matched male Wistar-Kyoto （WKY） normotensive rats were measured by tail-cuff method. Nitric oxide （NO） level and total antioxidant capacity （TAC） of blood serum were evaluated with Greiss reaction, ABTS and FRAP methods, respectively. Effects of superoxide dismutase （SOD） and NADPH oxidase inhibitor apocynin on endothelium-dependent vasodilatation were investigated in abdominal aorta rings. RT-PCR was used to measure the mRNA expressions of endothelial NO synthase （eNOS）, NADPH oxidase subunit p22^phox, and gp91^phox homologue nox4. Results SHR had lower TAC （P 〈 0.01） and NO level （P 〈 0.01）, and higher systolic blood pressure （P 〈 0.01） when compared with WKY rats. There were no differences in eNOS and p22^phox mRNA expression between SHR and WKY, whereas the mRNA expression of nox4 in SHR was significantly higher than that in WKY. In the SHR but not WKY rats, reduced endothelium dependent vasodilatation was reversed by a treatment with either SOD or apocynin. Conclusion These findings suggest that NADPH oxidase subunit gp91^phox homologue nox4 gene over-expression is correlated with the oxidative stress status of SHR. Pharmacologically modulating the function of NADPH oxidase significantly restored endothelium dependent vasodilatation of SHR. Thus, enhanced NADH/NADPH oxidase-dependent oxidative stress may contribute to endothelial dysfunction in this genetic model of hypertension.

关 键 词：NADPH氧化酶 自发性高血压大鼠 氧化应激 一氧化氮 

分 类 号：R-332[医药卫生] R345.4