芝麻素对自发性高血压大鼠海马nNOS和NADPH氧化酶亚单位p22phox、p47phox蛋白表达的调节作用  

Sesamin's regulatory effect on expression of oxidase subunits p22phox and p47phox of nN OS and NADPH at hippocampus in spontaneously hypertensive rats

作　　者：卢毅宁 沈媛媛[1] 杨解人[1] 

机构地区：[1]皖南医学院药理教研室 [2]芜湖市第一人民医院药学部

出　　处：《中国临床药理学与治疗学》2016年第9期989-994,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：安徽省自然科学基金项目(1308085QH145)

摘　　要：目的:探讨芝麻素(sesamin,Ses)对自发性高血压大鼠(SHR)海马神经元型一氧化氮合酶(nNOS)及烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶亚单位p22phox、p47phox蛋白表达的影响。方法:16周龄雄性SHR40只,随机分为SHR(0.5%羧甲基纤维素钠5mL·kg^(-1)·d^(-1),n=10)模型组、Ses高(160mg·kg^(-1)·d^(-1),n=10)和低(80mg·kg^(-1)·d^(-1),n=10)剂量组、卡托普利(30mL·kg^(-1)·d^(-1),n=10)阳性组。另设WKY(0.5%羧甲基纤维素钠5mL·kg^(-1)·d^(-1),n=10)正常对照组。各组于每日17时灌胃给药一次,连续12周。于末次给药后,禁食12h,腹腔麻醉,取脑,尼氏染色观察海马锥体细胞病理变化并计数;比色法测定海马组织丙二醛(MDA)、过氧化氢(H_2O_2)、超氧化物歧化酶(SOD)及总抗氧化能力(T-AOC)的含量;硝酸还原酶法测定海马组织NO含量;WesternBlot法检测海马组织nNOS、p22phox及p47phox蛋白表达。结果:芝麻素高、低剂量组对大鼠海马病理性损伤均有不同程度地改善,细胞数目增多(P<0.05或P<0.01),海马组织自由基(MDA、H_2O_2)减少,同时清除自由基和总抗氧化能力(SOD、T-AOC)明显升高(P<0.05或P<0.01);海马组织nNOS、p22phox和p47phox蛋白表达明显下调(P<0.05或P<0.01)。结论:Ses具有改善SHR海马损伤的作用,其机制与抑制海马nNOS及p22phox、p47phox所介导的氧化应激损伤有关。AIM： To investigate the effect of sesamin on expression of oxidase subunits p22phox and p47phox of nNOS and NADPH at hippocampus in spontaneously hypertensive rats（ SHR）. METHODS： 40 SHRs were randomly divided into groups of SHR model（ n = 10）,sesamin treatment in diverse dosage（ 80 and 160 mg·kg^-1·d^-1,n = 10）and captopril intervention（ 30 mg·kg^-1·d^-1,n =10）,and Wistar-Kyoto rats（ WKY,n = 10） were included as negative controls. All rats were intragastrically administrated with the drugs once a day at17： 00 p. m. for 12 consecutive weeks. Change of rat hippocampal neurons was detected via Nissl ＇s staining,MDA,H2O2,SOD,T-AOC levels and NO amount were examined in hippocampal homogenate and the expressions of nNOS,p22phox and p47phox protein were examined by Western blotting. RESULTS： Neuronal damages at hippocampus were relieved and the number of neuron increased in SHRs treat with sesamin（ 80 and 160 mg·kg^-1·d^-1） in different hippocampal regions significantly（ P〈0. 05 or P〈0. 01）. Levels of MDA,H2O2,SOD and NO amount in hippocampal homogenate were also significantly reduced（ P〈0. 05 or P〈0. 01）. Expressions of nNOS,p22phox and p47phox protein were significantly reduced and the SOD and T-AOC levels were improved significantly in hippocampal homogenate in SHR rats（ P〈0. 05 or P〈0. 01）.CONCLUSION： Sesamin can decrease the expression of nNOS,p22phox and p47phox protein to reduce oxidative stress at hippocampus in SHRs,suggesting that it has protective effect on hippocampal damage in SHRs.

关 键 词：芝麻素 自发性高血压大鼠 海马 神经元型一氧化氮合酶 NADPH氧化酶 氧化应激 

分 类 号：R965.2[医药卫生—药理学]