改善氧化/抗氧化应激平衡及NET和5-HTT表达与瑞波西汀抗抑郁作用有关

目的探讨瑞波西汀抗慢性轻度不可预见性刺激(CUMS)致大鼠抑郁症行为与机体氧化/抗氧化应激平衡以及去甲肾上腺素转运体(NET)和5-羟色胺转运体(5-HTT)表达的关系。方法♂SD大鼠60只,随机分为正常对照组(NG)、模型组(MG)、瑞波西汀(0.7 mg.kg-1.d-1)灌胃的模型组(RMG)和正常对照组(RNG)。采用孤养结合CUMS方式建立大鼠抑郁模型。以开场实验与糖水消耗实验评价大鼠抑郁行为,生物化学方法检测大鼠血清丙二醛(MDA)含量及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活力,RT-PCR法测定脑桥NET和海马5-HTT mRNA表达;光镜观察HE染色海马切片的病理形态改变。结果与NG组相比,MG组大鼠在开场实验中水平得分、垂直得分和理毛次数以及糖水消耗均明显降低,血清MDA含量升高,SOD和CAT活力及NET和5-HTT表达均下降,海马神经细胞出现明显核固缩和染色加深;给予瑞波西汀明显阻遏CUMS诱导的上述变化,但对正常组大鼠无影响。结论瑞波西汀可能通过逆转氧化/抗氧化应激系统失衡,增加NET和5-HTT的表达而产生抗抑郁作用。     

丙戊酸钠抗抑郁作用涉及改善氧化应激平衡和提升脑源性神经营养因子表达

目的:探讨丙戊酸钠减轻慢性不可预见刺激(CUS)致大鼠抑郁行为是否与改善机体氧化应激功能及脑源性神经营养因子(BDNF)表达有关.方法:雄性SD大鼠60只,随机分为对照组(CG),模型组(MG),丙戊酸钠灌胃正常组(VAPC)和丙戊酸钠灌胃模型组(VAPM).以开场试验和强迫游泳试验评价大鼠焦虑抑郁行为;采用常规生物化学方法测定大脑皮质丙二醛(MDA)含量及超氧化物歧化酶(SOD)和过氧化氢酶(CAT)活力;荧光定量PCR和Western blot检测海马脑源性神经营养因子(BDNF) mRNA和蛋白表达.结果:与CG组相比,MG组大鼠开场试验水平得分和垂直得分明显降低,强迫游泳试验不动时间显著延长,MDA含量升高,SOD及CAT活力明显下降,海马BDNF mRNA和蛋白表达均明显降低.给予丙戊酸钠可明显阻遏上述变化,但对正常大鼠无明显影响.结论:CUS致大鼠焦虑抑郁行为与体内氧化及抗氧化失衡,海马BDNF表达减少有关;丙戊酸钠能阻遏这种变化,从而显示减轻CUS所致大鼠焦虑抑郁行为作用.     

文拉法辛抗CUMS致大鼠抑郁行为涉及阻遏海马TH和TPH表达下调

目的 探讨慢性轻度不可预见刺激（Chronic unpredictable mild stress,CUMS）致大鼠抑郁行为与海马色氨酸羟化酶（Tryptophan hydroxylase TPH）和酪氨酸羟化酶（tyrosine hydroxylase, TH）表达关系及文拉法辛的干预作用。方法 雄性SD大鼠64只,随机分为对照组（NG）、模型组（MG）、文拉法辛灌胃正常组（WNG ）、文拉法辛灌胃模型组（ WMG）。采用孤养结合CUMS方式建立大鼠抑郁症模型;以开场实验和强迫游泳实验评价大鼠焦虑抑郁行为;生物化学方法检测大鼠皮层超氧化物歧化酶（Superoxide dismutase,SOD）活力以及丙二醛（Malondialdehyde , MDA）含量;荧光定量PCR和western-blot分别测定海马TPH、TH mRNA和蛋白表达。结果 与NG组相比,MG组大鼠开场实验水平得分、垂直得分明显降低,强迫游泳不动时间显著延长,MDA含量升高, SOD活力及TPH、TH mRNA和蛋白表达均明显下降;给予文拉法辛可明显阻遏CUMS诱导的上述变化,但对正常大鼠无影响。结论 CUMS致大鼠抑郁行为与海马TH和TPH表达下调有关;文拉法辛能阻遏这种表达下调,改善大鼠焦虑和抑郁症状。     

帕罗西汀抗抑郁作用涉及改善氧化应激状态、HPA轴功能和海马脑源性神经营养因子表达

目的:研究帕罗西汀抗慢性轻度不可预见刺激(CUMS)致大鼠抑郁症作用与调节氧化应激平衡和下丘脑-垂体-肾上腺皮质(HPA)轴功能及脑源性神经营养因子(BDNF)表达的关系。方法:♂SD大鼠60只,随机分为正常对照组(NG)、模型组(MG)、帕罗西汀(1.8mg.kg-1.d-1)灌胃处理模型组及对照组。采用孤养结合CUMS方式建立大鼠抑郁症模型。以开场实验及糖水消耗试验评价大鼠抑郁行为,试剂盒测定血清丙二醛(MDA)含量及过氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性变化;放射免疫法分析血清皮质酮(CORT)浓度,RT-PCR法测定大鼠海马BDNF及下丘脑CRFmRNA表达。结果:与NG组相比,MG组大鼠在开场实验中水平得分、垂直得分和理毛次数以及糖水消耗均明显降低,血清MDA含量明显升高,SOD和CAT活性降低,血清COTR含量及下丘脑CRF表达明显升高,海马BDNF表达降低。给予帕罗西汀能够显著阻遏CUMS诱导的上述变化,但对正常组大鼠无明显影响。结论:帕罗西汀抗抑郁作用可能与减轻CUMS所致氧化应激损伤和改善HPA轴功能及阻遏神经细胞BDNF表达降低有关。     

咖啡酸对慢性应激大鼠的抗抑郁作用

目的探讨咖啡酸对慢性应激大鼠的抗抑郁作用。方法采用各种慢性不可预见轻微刺激建立大鼠抑郁模型。21 d后,ig给予大鼠咖啡酸10,30和50 mg.kg-1,连续21 d。通过旷场实验检测中央格停留时间、水平活动和垂直活动情况,通过强迫游泳实验检测大鼠静止不动行为百分比(PI);检测海马超氧化物歧化酶(SOD)活性与丙二醛(MDA)含量。结果与正常对照组相比,模型组大鼠在旷场实验中央格停留时间增长,水平活动和垂直活动减少,强迫游泳静止不动状态增加,SOD活性显著降低,MDA含量显著升高(P<0.01)。与模型组相比,咖啡酸10～50 mg.kg-1组能够显著缩短停留时间(P<0.05)、增加垂直活动(P<0.01),但对水平活动无明显影响。模型组PI为(79.69±15.84)%,咖啡酸10～50 mg.kg-1组PI显著降低,分别为(16.00±2.11)%,(10.33±2.92)%和(7.33±2.63)%。与正常对照组相比,模型组SOD酶活性显著降低,MDA含量显著增加(P<0.01),与模型组相比,咖啡酸10～50 mg.kg-1能够显著增加SOD酶活性,分别为模型组的1.50,2.46和2.59倍(r=0.915,P<0.01);MDA含量显著降低,分别为模型组的18.64%,11.37%和6.35%(P<0.01),且呈剂量依赖性(r=0.982,P<0.01)。咖啡酸与舍曲林5 mg.kg-1的作用相似。结论咖啡酸对慢性应激大鼠有一定的抗抑郁作用。     

CUS致大鼠抑郁行为涉及TPH2、DDC及MAO-A异常表达的实验研究

目的探讨慢性不可预见刺激(chronically unpredicted stress,CUS)致大鼠抑郁行为与端脑和海马色氨酸羟化酶2(tryptophan hydroxylase-2,TPH2)、多巴脱羧酶(dopa-decarboxylase,DDC)及单胺氧化酶A(monoamine oxidase-A,MAOA)mRNA及蛋白表达的关系。方法 30只♂SD大鼠随机分为模型组(MG)与对照组(CG),每组15只。采用孤养结合CUS连续刺激28 d建立大鼠抑郁模型;以开场实验和强迫游泳实验评价大鼠抑郁行为;采用实时荧光定量PCR与Western blot方法分别检测大鼠端脑和海马TPH2、DDC、MAO-A mRNA及蛋白表达。结果与对照组大鼠相比,模型组大鼠开场实验运动得分明显降低(P<0.01)、强迫游泳不动时间明显延长(P<0.01);端脑和海马TPH2和DDC mRNA及蛋白表达明显下降(P<0.01,P<0.05)、MAO-A mRNA及蛋白表达明显升高(P<0.01,P<0.05)。结论CUS诱导大鼠产生抑郁症样行为,其机制可能与TPH2、DDC及MAO-A异常表达有关。     

艾司西酞普兰和文拉法辛缓释剂治疗抑郁症的疗效及耐受性比较

目的比较艾司西酞普兰和文拉法辛缓释剂治疗抑郁症患者的疗效、耐受性和起效时间。方法选择住院及门诊中重度抑郁症患者130例,进行为期8周的艾司西酞普兰（10～20mg／d,n=65）和文拉法辛缓释剂（75～150mg／d,n：65）治疗,采用蒙格马利一阿斯伯格抑郁评定量表（MADRS）进行疗效评定。结果第8周时,应用MADRS评分,两组疗效相似;艾司西酞普兰组患者获得持续缓解的速度明显快于文拉法辛组;文拉法辛组出现恶心、便秘和多汗较多（P〈0．05）,停药患者较多（P〈0．01）。结论艾司西酞普兰和文拉法辛缓释荆治疗抑郁症患者疗效相似,而艾司西酞普兰耐受性和起效速度更佳。     

人参皂苷Rg1的抗抑郁作用及对突触超微结构的影响

目的观察人参皂苷Rg1的抗抑郁作用及慢性应激对额前皮质区突触超微结构的改变。方法采用慢性温和不可预见性应激(chronic unpredictable mild stress,CUMS)的方法建立大鼠抑郁模型。造模同时给予人参皂苷Rg1(5、10和20 mg·kg-1)和度洛西汀(10 mg·kg-1),每天1次,连续28 d。用强迫游泳和糖水消耗的行为学方法检测大鼠的抑郁行为学变化,电子显微镜观察应激后大鼠额前皮质区突触超微结构的变化。结果与对照组相比,慢性应激大鼠在强迫游泳实验中的不动时间明显增加(P<0.01),糖水偏好实验中的糖水消耗百分比明显降低(P<0.01);电镜观察结果显示模型组大鼠额前皮质区突触超微结构异常,突触前膜的突触囊泡密度减小,突触后膜致密物厚度也减少。与模型组相比,人参皂苷Rg1能明显改善慢性应激大鼠的抑郁行为,改善大鼠额前皮质区突触超微结构。结论人参皂苷Rg1对CUMS诱导的大鼠抑郁行为和额前皮质区突触超微结构的异常有明显的改善作用。     

藏药佐太的抗抑郁抗焦虑作用研究

目的 观察藏药佐太的抗抑郁和抗焦虑作用,并探讨其可能作用机制。方法 1）初步评价实验：在小鼠ig给予6.07、60.70、303.49、606.97 mg/kg佐太14 d后,通过强迫游泳实验和开场实验初步评价佐太对抑郁和焦虑的影响,同时通过检测小鼠血清中5-羟色胺（5-HT）和去甲肾上腺素（NE）水平来探讨佐太产生影响的可能作用机制。2）不可预测性慢性温和应激模型（CUMS）实验：建立CUMS模型,ig给予6.07、60.70、606.97 mg/kg佐太后,通过小鼠体质量变化、糖水偏爱实验、小鼠悬尾实验、开场实验和埋珠实验评价佐太对CUMS模型小鼠的抗抑郁和抗焦虑作用,同时检测小鼠血清中皮质酮（CORT）、促肾上腺皮质激素（ACTH）和下丘脑中促肾上腺皮质激素释放激素（CRH）水平,测定佐太对CUMS模型小鼠下丘脑-垂体-肾上腺（HPA）轴的影响。结果 1）佐太能够显著减少小鼠强迫游泳实验中不动时间（6.07、60.70、303.49、606.97 mg/kg）;增加小鼠在开场实验中中央区停留时间百分率（606.97 mg/kg）和中央区运动百分比（303.49、606.97 mg/kg）;增加小鼠血清中5-HT（6.07、606.97 mg/kg）和NE（6.07、303.49、606.97 mg/kg）水平。2）CUMS实验中,与对照组比较,经过42 d CUMS慢性应激小鼠表现出明显的抑郁和焦虑样行为,包括糖水偏爱率的降低、悬尾不动时间显著增加、开场实验中运动时间、中央区域停留时间及运动距离的减少和周边区域运动距离的增加、埋珠实验中埋珠个数的增加。而ig给予佐太（6.07、60.70、606.97 mg/kg）能够显著改善CUMS模型引起的上述症状,并且佐太（6.07、60.70 mg/kg）能够显著降低CORT、ACTH和CRH水平,抑制CUMS模型引起的HPA轴亢进。结论 佐太具有一定的抗抑郁和抗焦虑作用,并且其作用机制可能与升高5-HT、NE水平和抑制HPA轴亢进有关。     

文拉法辛对慢性应激抑郁模型大鼠脑内ERK1、ERK2磷酸化水平及Egr-1表达的影响

目的:探讨文拉法辛对慢性应激抑郁模型大鼠不同脑区细胞外信号调节激酶(ERK1/ERK2)含量和活性及即刻早期反应因子(Egr-1)的影响。方法:以旷场试验得分评价大鼠行为,将成年SD大鼠随机分为正常对照组、抑郁模型组、抑郁模型+文拉法辛混悬液低、中、高剂量(15、30、60 mg.kg-1.d-1)灌胃组。用慢性轻度不可预见性应激加分养方法建立抑郁大鼠模型,采用蛋白印迹法检测大鼠前额叶、海马、下丘脑、纹状体磷酸化p-ERK1、p-ERK2和非磷酸化ERK1、ERK2蛋白及Egr-1的表达水平。结果:不同剂量文拉法辛组旷场行为得分较给药前有明显升高(P<0.01),而模型组给药前后无改善(P>0.05);除前额叶部位不同剂量文拉法辛组p-ERK1、p-ERK2表达水平较模型组高外,其余各部位各组p-ERK1、p-ERK2、ERK1、ERK2、Egr-1表达水平比较均无显著性差异(P>0.05)。结论:文拉法辛可能通过上调前额叶部位ERK1、ERK2磷酸化水平,明显改善慢性应激抑郁模型大鼠的抑郁样行为。     

5-羟色胺转运蛋白基因多态性与抗抑郁药临床疗效的关系

目的:研究南京地区人群中5-羟色胺转运蛋白(5-HTT)基因多态性与血浆5-羟色胺(5-HT)浓度及选择性5-羟色胺再摄取抑制剂(SSRIs)的抗抑郁临床疗效是否存在相关性。方法;采用聚合酶链式反应(PCR)多态性分析技术对132例抑郁症患者和100名健康者进行基因型分析;HPLC-ECD法分析血浆中5-HT浓度;用汉密尔顿抑郁量表(HAMD)评定抗抑郁药的疗效。结果:抑郁症5-HTT基因基因型频率(LL24.2％,LS44.7％,SS31.1％)、等位基因频率(L46.59％,S53.41％);与正常对照组基因型频率(LL29.0％,LS47.0％,SS24.0％)、等位基因频率(L52.5％,S47.5％)比较无显著性差异(P>0.05);不同基因型抑郁症患者治疗前HAMD总分有显著差异,F=6.48,P=0.0021:经4wk SSRIs类抗抑郁药治疗后,HAMD总分均显著下降,减分值有显著差异,F=3.38,P=0.037;治疗前不同基因型患者5-HT浓度有显著差异,F=5.38,P=0.005 7;4wk治疗后,血浆中5-HT浓度均升高,不同基因型的增高值有明显差异,F=23.55,P<0.01。结论:南京地区人群中5-HTT基因多态性与抑郁症的发病不存在相关性,但与抑郁症疾病严重程度和SSRIs治疗效应存在显著的相关性,这一区域的基因型可能成为抑郁症患者实现个体化治疗的一个参考指标。     

Toxic metals and oxidative stress part I: mechanisms involved in metal-induced oxidative damage

Toxic metals (lead, cadmium, mercury and arsenic) are widely found in our environment. Humans are exposed to these metals from numerous sources, including contaminated air, water, soil and food. Recent studies indicate that transition metals act as catalysts in the oxidative reactions of biological macromolecules therefore the toxicities associated with these metals might be due to oxidative tissue damage. Redox-active metals, such as iron, copper and chromium, undergo redox cycling whereas redox-inactive metals, such as lead, cadmium, mercury and others deplete cells' major antioxidants, particularly thiol-containing antioxidants and enzymes. Either redox-active or redox-inactive metals may cause an increase in production of reactive oxygen species (ROS) such as hydroxyl radical (HO.), superoxide radical (O2.-) or hydrogen peroxide (H2O2). Enhanced generation of ROS can overwhelm cells' intrinsic antioxidant defenses, and result in a condition known as "oxidative stress". Cells under oxidative stress display various dysfunctions due to lesions caused by ROS to lipids, proteins and DNA. Consequently, it is suggested that metal-induced oxidative stress in cells can be partially responsible for the toxic effects of heavy metals. Several studies are underway to determine the effect of antioxidant supplementation following heavy metal exposure. Data suggest that antioxidants may play an important role in abating some hazards of heavy metals. In order to prove the importance of using antioxidants in heavy metal poisoning, pertinent biochemical mechanisms for metal-induced oxidative stress should be reviewed.     

天麻素对癫疒间大鼠海马氧化应激水平的影响

目的研究天麻素对戊四氮(PTZ)致疒间大鼠海马氧化应激水平的影响。方法将30只成年Wistar大鼠随机分为正常对照(NC)组、癫疒间模型(PTZ)组、天麻素(GS)组,观察三组大鼠的行为学和脑电图的变化,采用比色法检测大鼠海马超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力和丙二醛(MDA)含量的变化。结果与PTZ组比较,GS组大鼠癫疒间发作程度减轻,脑电图明显改变,海马组织中SOD和GSHPx活力增加,M DA含量明显减少(P<0.01)。结论天麻素可通过增加癫疒间大鼠海马SOD、GSH-Px活力、抑制M DA的产生,从而影响氧化应激水平,达到对抗癫疒间的效果。     

Heroin-administered mice involved in oxidative stress and exogenous antioxidant-alleviated withdrawal syndrome

Heroin has been shown to elevate dopamine (DA) level. It is well known that an increase in DA oxidative metabolism leads to increased reactive oxygen species (ROS) formation, and thus, ROS have been frequently associated with neuronal cell death due to damage to carbohydrates, amino acids, phospholipids, and nucleic acids. This study investigated whether there are oxidative stress and effects of exogenous antioxidants in heroin-administered mice. The heroin-dependent mice model was made via intraperitoneal injection. Oxidative damage of DNA, protein, and lipid was measured by analysis of single cell electrophoresis, the 2,4-dinitrophenylhydrazine method, and thiobarbituric acid method respectively. The activities of antioxidative enzymes and total antioxidant capacity were assayed by spectrophotometry. After administration with heroin, the mice not only showed decrease of total antioxidant capacity in serum and antioxidant enzymes such as superoxide dismutase, catalase, and glutathione (GSH) peroxidase in brain, but also exhibited the oxidative damages of DNA, protein and lipid. On the other hand, exogenous antioxidants could restrain the oxidative stress, even alleviate withdrawal syndrome in heroin-administered mice. Our results also imply a possibility that ROS may participate in the whole process of dependence and withdrawal of heroin. Therefore, strategies of blocking oxidative stress may be useful in the development of therapy for opiate abuse.     

白藜芦醇抑制人牙龈成纤维细胞炎症和氧化应激的机制研究

目的 探讨白藜芦醇（RSV）对牙龈卟啉单胞菌脂多糖（LPS）诱导的人牙龈成纤维细胞（HGF）的炎症和氧 化应激的调节作用。方法 原代培养HGF,将细胞分为实验1和实验2：实验1细胞分为对照组、LPS组、RSV 20 μmol/L 组、RSV 40 μmol/L组、RSV 80 μmol/L组、LPS+RSV 20 μmol/L组、LPS+RSV 40 μmol/L组和LPS+RSV 80 μmol/L组;实 验2细胞分为对照组、LPS组、LPS+RSV 40 μmol/L 组、LPS+RSV 40 μmol/L+E5564组和LPS+E5564组。通过CCK-8 法评估细胞活力。利用酶联免疫吸附试验测定白细胞介素（IL）-1β、IL-6、IL-8、肿瘤坏死因子（TNF）-α、超氧化物歧 化酶（SOD）、丙二醛（MDA）和谷胱甘肽过氧化物酶（GSH-Px）水平。通过Western blot分析测量蛋白的表达水平。结 果 20、40和80 μmol/L RSV对HGF均没有明显的细胞毒性作用。在LPS诱导的HGF细胞中,40和80 μmol/L RSV 通过下调IL-1β、IL-6、IL-8和TNF-α的表达减弱炎症反应,降低了MDA的含量,并显著提高了SOD的水平,80 μmol/L RSV显著提高了GSH-Px水平（P＜0.05）。此外,20、40和80 μmol/L RSV可诱导Toll样受体4（TLR4）/MyD88/NF-κB 信号通路的失活,其均可降低TLR4、MyD88和p-p65蛋白的表达水平（P＜0.05）。TLR4抑制剂（E5564）通过下调IL- 1β、IL-6、IL-8和TNF-α的产生以及上调GSH-Px水平进一步增强了RSV对炎症和氧化应激损伤的缓解作用（P＜ 0.05）。结论 RSV可通过诱导TLR4/MyD88/NF-κB信号通路失活,减轻LPS导致的HGF炎症和氧化应激损伤。     

S-Allylcysteine prevents amyloid-beta peptide-induced oxidative stress in rat hippocampus and ameliorates learning deficits

The effects of S-allylcysteine on oxidative damage and spatial learning and memory deficits produced by an intrahippocampal injection of amyloid-beta peptide 25-35 (Abeta(25-35)) in rats were investigated. The formation of reactive oxygen species, lipid peroxidation and the activities of the antioxidant enzymes superoxide dismutase and glutathione peroxidase were all measured in hippocampus 120 min after Abeta(25-35) injection (1 microl of 100 microM solution), while learning and memory skills were evaluated 2 and 35 days after the infusion of Abeta(25-35) to rats, respectively. Abeta(25-35) increased both reactive oxygen species and lipid peroxidation, whereas pretreatment with S-allylcysteine (300 mg/kg, i.p.) 30 min before peptide injection decreased both of these markers. In addition, Abeta(25-35)-induced incorrect learning responses were prevented in most of trials by S-allylcysteine. In contrast, enzyme activities were found unchanged in all groups tested. Findings of this work: (i) support the participation of reactive oxygen species in Abeta(25-35)-induced hippocampal toxicity and learning deficits; and (ii) suggest that the protective effects of S-allylcysteine were related to its ability to scavenge reactive oxygen species.     

Neonatal isolation changes the expression of IGF-IR and IGFBP-2 in the hippocampus in response to adulthood restraint stress

Early adverse experiences are thought to contribute to the development of stress vulnerability, and to increase the onset of stress-related psychiatric disorders in stressful environments in adulthood. One plausible molecular mechanism of stress vulnerability is the modulation of neurotrophic factor signal transduction in the hippocampus by early adversity. In the present study we investigated the influence of neonatal isolation (NI) with or without adulthood single restraint stress (SRS) on the expression of several growth factor-related genes in the rat hippocampus using a cDNA microarray, real-time quantitative PCR, and Western blot. We found that hippocampal insulin-like growth factor-I receptor (IGF-IR) mRNA levels and immunoreactivity, and IGF binding protein-2 (IGFBP-2) mRNA levels were significantly lower in response to SRS in NI rats compared with rats without NI. Immunohistochemical analyses revealed that hippocampal IGF-IR immunoreactivity in the CA1 and CA3 pyramidal cell layers, and in the dentate gyrus granule cell layer of NI rats subjected to SRS was significantly lower compared with rats subjected to SRS. In addition, the hippocampal levels of IGF-IR mRNA were significantly lower in adult rats subjected to NI. These findings indicate that NI down-regulates IGF signal transduction under basal and stressful conditions in later life. Since the activation of IGF signalling plays a role in the development and neuroprotection of the central nervous system, the down-regulation of IGF signal transduction induced by NI may be, at least in part, involved in the development of adulthood stress vulnerability, which in turn precipitates the onset of depression.     

NADPH氧化酶对自发性高血压大鼠体内氧化应激的影响

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。