Salt and nitric oxide inhibition induced hypertension: the role of prostacycline and 8-isoprostane

Renal prostacycline (PGI(2)) and oxidative stress are known to be important factors that effect the natriurezis and diuresis. 8-iso prostaglandin F(2)α± (8-isoprostane), a member of F(2)-isoprostanes, is formed from the nonenzymatic reaction of arachidonic acid and oxygen radicals in vivo and in vitro, and also it is a marker of oxidative stress in vivo. The aim of this study is to determine the role of renal PGI(2) and 8-isoprostane in a salt and nitric oxide (NO) inhibition-induced hypertension model. Rats were distributed equally among four groups (n = 6 per group). Control rats were given normal salt diet (0.32%); high-salt (HS) rats were given high salt diet (3.2%); NG-nitro-L-arginine (L-NNA) rats were given normal salt diet and 25 mg/kg L-NNA; HS+L-NNA rats were given high salt diet and 25 mg/kg L-NNA. Rats were placed in individual metabolic cages for 17 days. Systolic blood pressure (SBP) was measured at days initial, 7th and 14th .Urinary 8-isoprostane and PGI(2) levels were analyzed. Salt- loading alone did not change SBP values. The average SBP in L-NNA and HS+L-NNA groups were shown to significantly enhance compared to initial and day 7th in the same groups, respectively. The levels of 8-isoprostane in the HS+L-NNA group was significantly enhanced compared to the other groups. L-NNA or HS diet alone did not change the levels of 8-isoprostane compared to the control group. L-NNA alone did not change PGI(2) levels in urine compared to the control. PGI(2) levels in the HS, and the HS+L-NNA group was significantly higher compared to the control group. This study concluded that NOS inhibition plus salt-loading induced oxidative stress and increased renal PGI(2). Also, it is suggested that augmented oxidative stress may aggravate the hypertension. But the renal synthesis of PGI(2) is increased in order to augment the diuresis and natriuresis without the effect of blood pressure (BP).     

High salt intake accelerated cardiac remodeling in spontaneously hypertensive rats: time window of left ventricular functional transition and its relation to salt-loading doses

Salt-loading is an accelerator of hypertensive left ventricular (LV) remodeling. The relationship between salt-loading doses and the time window in which a transition from compensated to decompensated LV hypertrophy occurs in spontaneously hypertensive rats (SHR) is unclear. Eight-week-old male SHR and Wistar Kyoto rats (WKY) were randomized to receive normal (0.5% NaCl) and high salt diets (4% or 8% NaCl) for 12 weeks. Left ventricular remodeling was dynamically determined by echocardiography. LV invasive hemodynamics and morphologic staining [collagen deposition, cardiomyocte hypertrophy, DNA damage (8-hydroxy-2-deoxyguanosine, 8-OHdG) and apoptosis] were performed at time of sacrifice. Cardiac malonyldialdehyde (MDA) level was measured by ELISA. No differences between 4% and 8% salt diets, in terms of blood pressure (BP) levels, heart mass index, and myocardial fibrosis were observed either in SHR or in WKY. In high salt-loaded SHR, the LV ejection fraction and wall thickness peaked at 8 weeks after salt-loading, parallel with a progressive enlargement of the LV chamber size. Furthermore, when compared to 4% salt SHR, LV functions were significantly compromised in 8% salt SHR, accompanied by more prominent cardiomyoctye hypertrophy, oxidative stress (and related DNA damage), and apoptosis. Salt-loading for 12 weeks with 8% NaCl diet is more efficient to induce LV dysfunction than 4% NaCl diet does in SHR, possibly by initiating increased oxidative stress and resultant cardiac damage. Moreover, 8 to 12 weeks after 8% salt-loading is the key time window in which a transition from compensated to decompensated LV hypertrophy occurs.     

不同尿酸浓度与氧化应激和内皮损伤指标研究

目的 观察不同血尿酸浓度下氧化应激指标变化,探讨高尿酸引起血管内皮功能损伤的机制.方法 选择男性正常血尿酸及高尿酸血症病例,根据血尿酸值分为5组,每组50例左右,分别测定血浆丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH·Px)、NO、纤溶酶原激活抑制剂-1(PAI-1)、内皮素-1(ET-1)及各项生化指标.结果 尿酸≥380 μmol/L时,MDA、SOD、GSH-Px、PM-1、ET-1均明显增加,NO明显下降(P值均<0.05),但当尿酸≥420 μmol/L时,SOD、GSH-Px明显下降;回归分析显示PAI-1与MDA、尿酸、HOMA胰岛素抵抗指数(HOMA-IR)、TG正相关,与SOD、NO负相关(t=-3.64～6.08,P<0.05);ET-1与MDA、尿酸、HOMA-IR正相关,与NO、GSH-Px、SOD负相关(t=-4.75～6.35,P<0.05).结论 男性血尿酸超过380 umol/L时引起氧化应激,氧化应激、血尿酸、胰岛素抵抗参与了内皮功能紊乱的形成.     

The effects of estrogen and raloxifene treatment on antioxidant enzymes in brain and liver of ovarectomized female rats

Recent studies documented that estrogen have antioxidant properties in-vitro, there are conflicting results on the effect of estrogen in vivo. We aimed to investigate the effects of estradiol and Raloxifene on the antioxidant enzyme [superoxide dismutase (SOD) and catalase (CAT)] activities and MDA levels in brain and liver homogenates of ovariectomized female rats. Twelve weeks after ovariectomy, female Sprague-Dawley rats (n = 26) were divided into three groups: (1) Ovariectomized placebo group (n = 6) was given physiologic saline. (2) Estrogen group (n = 10) was given Ethynyl estradiol, 0.1 mg/kg sc. (3) Raloxifene group (n = 10) was given raloxifene, 1 mg/kg sc during 8 weeks. Ten rats were used as naive controls without any treatment (Sham operated group, n = 10). Ovariectomy lead to an increase in the CAT activities in liver tissue samples compared to the sham group (p = 0.056, Mann-Whitney test). While estrogen treatment reversed to normal levels of CAT activities, raloxifene remained as ineffective. Superoxide dismutase activities and MDA levels in liver were remained unchanged in all groups. There was no significant change in the brain tissue SOD and CAT activities between the control ovariectomy, estrogen treated, and raloxifen treated groups. We determined an increase in MDA levels in brain of ovariectmised rat (p = 0.02). While raloxifene treatment reversed to normal levels of MDA (p = estrogen treatment failed. Our data showed that estrogen may play a role in regulation of CAT and SOD activities in liver due to its antioxidative effects. We can suggest estrogen and raloxifene exert their antioxidative effects in brain rather than liver. Since Raloxifene's effect is more clear than estradiol, raloxifene may be suggested primarily for treatment and/or prevention of diseases which can be resulted from oxidative stress in postmenopausal women.     

肿瘤坏死因子α与一氧化氮在脑型疟疾发病中的作用

目的研究肿瘤坏死因子α（TNF-α）与一氧化氮（NO）在脑型疟疾（cerebral malaria,CM）发病中的作用。方法建立C57BL/6J小鼠CM动物模型,按文献方法检测发病过程中血清及脑组织TNF-α、NO及一氧化氮合酶（NOS）含量,同时观察地塞米松及NO合成抑制剂L-硝基精氨酸（L-NNA）对血清和脑组织中TNF-α和NO浓度的影响。结果CM模型组小鼠均发生CM,地塞米松组、L-NNA组小鼠及感染对照组小鼠至感染后第10d均未发生CM;CM模型组小鼠发病时脑组织、血清TNF-α、NO、NOS及脑组织含水量均高于感染第5d（P〈0.01）;CM模型组小鼠发病时和感染后第5d脑组织及血清TNF-α、NO、NOS和脑组织含水量均高于正常对照组及感染对照组（P〈0.01）;地塞米松组小鼠感染后第5d及第10d与同时间CM模型组比较,脑组织、血清TNF-α和脑组织含水量均显著下降（P〈0.01）;L-NNA组与CM模型组比较,脑组织及血清NO、NOS、脑组织含水量均显著降低（P〈0.01）。结论CM症状可能与小鼠脑组织NO过量有关,TNF-α主要通过NO起作用。使用地塞米松和L-NNA可降低体内NO浓度,预防CM发生。     

老年轻度认知障碍患者血清氧化应激状态与幽门螺杆菌感染的关系

目的 探讨老年轻度认知障碍(MCI)患者血清氧化应激状态与幽门螺杆菌(HP)感染的关系.方法 收集60岁以上老年人265例,分为4组:MCI(HP+)组、MCI(HP-)组、对照(HP+)组和对照(HP-)组.检测血清谷胱甘肽过氧化物酶(GSH-PX)、过氧化氢酶(CAT)和超氧化物歧化酶(SOD)等氧化应激指标,以及丙氨酸氨基转移酶(ALT)、血尿素、尿酸、总胆固醇(TC)、三酰甘油(TG)和糖化血红蛋白(HbAlc)等生化指标,统计学软件分析组间及多因素间关系. 结果(1)MCI组与对照组比较,HP阳性率差异无统计学意义;各组年龄、性别、ALT、血尿素、TC、TG和HbAlc比较,差异无统计学意义;(2)MCI(HP+)组GSH-PX和CAT活力分别为(894.4±53.9)U/L和(14.5±1.1)U/ml,与MCI(Hp-)组比较[(694.7±20.8)U/ml和(11.8±0.7)U/mL]显著增高(t=4.099、2.108,均P<0.05);对照(HP+)组cAT活力为(15.4±0.9)U/ml,与对照(HP-)组比较[(13.0±0.5)U/L]显著增高(t=2.251,P<0.05);GSH-pX活力MCI(HP+)组与对照(HP+)组[(603.8±24.1)U/L3比较显著增高(t=4.926,P<0.05);MCI(HP-)组与对照(HP-)组[(593.5±16.6)U/m1]比较显著增高(t=3.801,P<0.05).各组间SOD活力比较,差异无统计学意义;(3)多元逐步回归分析,GSH-PX与年龄呈负相关(β=-0.621,P<0.05),CAT与尿酸呈正相关(β=0.523,P<0.05). 结论 HP感染可能影响老年MCI患者与GSH-PX和CAT活力相关的氧化应激状态.     

基于Nrf2-Keap1-ARE信号通路探讨疏肝健脾方对肠易激综合征大鼠内脏敏感性的影响

目的基于核因子E2相关因子2(Nrf2)-Kelch样环氧氯丙烷相关蛋白-1(Keap1)-抗氧化反应元件(ARE)信号通路观察疏肝健脾方对肠易激综合征(IBS)大鼠内脏敏感性的影响。方法取30只SPF级雄性Wistar大鼠采用4%醋酸灌肠复合慢性心理应激法建立IBS大鼠模型,并随机分为模型组、疏肝健脾方组以及阳性对照组(匹维溴铵组),另取10只不予任何处理作为空白组。疏肝健脾方组按5 mL/kg的剂量给予疏肝健脾方,阳性对照组按2 mg/kg的剂量灌胃给匹维溴铵,空白组和模型组按5 mL/kg的剂量给0.9%氯化钠溶液,造模结束后以粪便含水率进行模型评价。给药结束后当天,对粪便含水率进行检测;比较大鼠内脏的敏感性;HE染色检测大鼠结肠组织形态;比较血清胃肠激素水平;检测大鼠血清中氧化应激指标;免疫荧光法检测ZO-1、Occludin蛋白的损伤;Western blotting检测Nrf2-Keap1-ARE通路蛋白表达。结果与空白组相比,模型组大鼠的粪便含水量,血清中SP、SS、MDA水平,结肠组织中p-Nrf2、p-Keap1、p-ARE蛋白表达水平显著升高;腹部抬起和背部拱起程度,血清中GAS、MTL、SOD、NO水平,结肠黏膜中ZO-1、Occludin表达量显著降低。与模型组相比,疏肝健脾组和阳性对照组大鼠治疗后的粪便含水量,血清中SP、SS、MDA水平,结肠组织中p-Nrf2、p-Keap1、p-ARE蛋白表达水平显著下降;腹部抬起和背部拱起程度,血清中GAS、MTL、SOD、NO水平,结肠黏膜中ZO-1、Occludin表达量显著上升。结论疏肝健脾方能够有效改善大鼠IBS情况,降低氧化应激水平及结肠黏膜紧密连接蛋白的损伤程度,其机制可能与Nrf2-Keap1-ARE信号通路的调控有关。     

SOD在肾缺血再灌注损伤大鼠肺内的表达变化

目的 观察肾缺血再灌注损伤大鼠肺内超氧化物歧化酶(superoxide dismutase,SOD)的表达变化,探讨SOD在抗氧化应激反应中的作用.方法 Wistar大鼠切除右肾,无损伤动脉夹夹闭左肾动脉,建立大鼠肾缺血再灌注损伤模型.再灌注24 h后取材(肺、肾、血).酶偶联速率法和苦味酸法分别检测血尿素氮(blood urea nitrogen,BUN)、血清肌酐(serum creatinine,SCr)浓度;HE染色法观察大鼠肾形态;硫代巴比妥酸比色法检测肺内丙二醛(malondialdehyde,MDA)的含量;采用Western blot和RT-PCR方法分别测定大鼠肺组织内抗氧化酶SOD的蛋白与mRNA表达水平.结果 HE结果显示肾缺血再灌注损伤组大鼠的肾组织受损明显.与对照组相比,肾缺血再灌注损伤组血清中的BUN和SCr、肺组织中的MDA含量均明显升高(P值均＜0.01),SOD的蛋白与mRNA的表达水平均明显升高(P值均＜0.01).结论 肾缺血再灌注损伤大鼠的肺组织发生了过氧化损伤.SOD在肾缺血再灌注损伤大鼠的肺组织内发挥了抗氧化应激的作用.     

<Emphasis Type="Italic">Emblica officinalis</Emphasis> Exerts Antihypertensive Effect in a Rat Model of DOCA-Salt-Induced Hypertension: Role of (p) eNOS,NO and Oxidative Stress

Emblica officinalis (EO) has antioxidant properties that could improve redox-sensitive vascular, cardiac and renal changes associated with deoxycorticosterone acetate/1% NaCl high salt (DOCA/HS)-induced hypertension. We determined whether hydroalcoholic lyophilized extract of EO may influence DOCA/HS-induced hypertension by modulating activity of (p) eNOS and endogenous antioxidants. Hypertension was induced in rats by DOCA-salt (20 mg/kg, s.c.) twice weekly for 5 weeks and replacing drinking water with 1% NaCl solution. These rats received cotreatment of different doses of EO (75, 150 and 300 mg/kg/day) for 5 weeks. EO significantly decreased arterial blood pressure and heart rate along with cardiac and renal hypertrophy in a dose-dependent fashion as compared to DOCA control rats. Increased TBARS and decreased endogenous antioxidants including GSH, SOD and GSHPx activity in serum, heart and kidney tissues of hypertensive rats were also normalized. Furthermore, this antihypertensive activity of EO was also linked with increased serum NO, K⁺ levels and decreased Na⁺ levels. Moreover, EO robustly increased activated eNOS expression in heart. Our results demonstrate that EO reduces oxidative stress, prevents development and progression of hypertension as well as cardiac and renal hypertrophy in DOCA/HS-induced hypertension via modulation of activated eNOS, endogenous antioxidants, serum NO and electrolyte levels.     

Oxidative stress in portal hypertension-induced rats with particular emphasis on nitric oxide and trace metals

AIM: To investigate the oxidative-stress-related changes in rats with portal hypertension with particular emphasis on nitric oxide (NO) and trace metals. METHODS: Cirrhosis was induced by partial portal vein ligation (PVL) in Wistar rats. The lipid peroxidation marker (malondialdehyde, MDA), antioxidant defense enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), and agents known to have antioxidant features including nitric oxide (NO), zinc (Zn), copper (Cu) were determined both in serum and in liver tissue at 4 wk after surgery in PVL and sham-operated rats. Portal pressure of all experimental animals was measured. MDA was detected by thiobarbituric acid reactivity assay. SOD activity was determined by inhibition of nitroblue tetrazolium reduction with xanthine/xanthine oxidase used as a superoxide generator. CAT activity was determined by the breakdown of hydrogen peroxide. GSH concentrations were measured by using metaphosphoric acid for protein precipitation and 5'-5'-dithio-bis-2-nitrobenzoic acid for color development. NO was detected by the Griess method after reduction of nitrate to nitrite with nitrate reductase, and the concentrations of Zn and Cu were measured by a Shimadzu 680 AA atomic absorption spectrometer. Histopathological confirmation was done under light microscope. Statistical analyses were done by Student's t-test, and significance of the difference was tested by the unpaired Mann-Whitney test. P<0.05 was considered statistically significant. RESULTS: Histopathological studies confirmed PVL-induced cirrhotic changes. There was a statistically significant difference in portal pressure between PVL and control groups (P<0.001). The results showed significant increases in the levels of MDA and NO in both tissue and serum (P<0.05 and P<0.001, respectively in tissue; P<0.001 for each in serum), and Zn only in tissue (P<0.001) in rats with PVL compared with sham-operated rats. Besides, PVL rats exhibited reduced plasma and tissue GSH, CAT, SOD (P<0.001 for each). Serum and tissue Cu concentration did not change. CONCLUSION: Our findings suggest that PVL in rats induces important biochemical and molecular changes related to oxidative stress in the liver.     

氟斑牙发生与氧化应激的研究

目的探讨氟斑牙发生过程中是否存在氧化应激反应。方法80只SD大鼠按雌雄各半体重均等原则随机分为4组,即饮水氟含量50．00mg／L（H）组、25．00mg／L（M）组、12．50mg／L（L）组和0．08mg／L（C）组。饲养16周后处死大鼠,测血清及肝、肾组织中丙二醛（MDA）含量、超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽过氧化物（GSH—Px）活性。结果H、M组及部分L组大鼠下切牙釉质出现棕白相间条纹等典型氟斑牙症状。随着染氟剂量的增加,H、M、L组大鼠血清、肝MDA含量较C组有升高趋势（P〈0．01或P〈0．05）,血清及肝、肾SOD、CAT活性较C组有降低趋势（P〈0．01或P〈0．05）,GSH—Px活性变化无统计学意义（P〉0．05）。结论氟斑牙发生过程中大鼠体内可能存在氧化系统与抗氧化系统的失衡,氧化应激反应可能是氟中毒早期症状之一。     

Melatonin ameliorates chronic renal failure-induced oxidative organ damage in rats

Chronic renal failure (CRF) is associated with oxidative stress that promotes production of reactive oxygen species (ROS). Melatonin, the chief secretory product of the pineal gland, was recently found to be a potent free radical scavenger and antioxidant. The aim of this study was to examine the role of melatonin in protecting the aorta, heart, corpus cavernosum, lung, diaphragm, and kidney tissues against oxidative damage in a rat model of CRF, which was induced by five of six nephrectomy. Male Wistar albino rats were randomly assigned to either the CRF group or the sham-operated control group, which had received saline or melatonin (10 mg/kg, i.p.) for 4 wk. CRF was evaluated by serum blood urea nitrogen (BUN) level and creatinine measurements. Aorta and corporeal tissues were used for contractility studies, or stored along with heart, lung, diaphragm, and kidney tissues for the measurement of malondialdehyde (MDA, an index of lipid peroxidation), protein carbonylation (PC, an index for protein oxidation), and glutathione (GSH) levels (a key antioxidant). Plasma MDA, PC, and GSH levels and erythrocytic superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities were studied to evaluate the changes of antioxidant status in CRF. In the CRF group, the contraction and the relaxation of aorta and corpus cavernosum samples decreased significantly compared with controls (P < 0.05-0.001). Melatonin treatment of the CRF group restored these responses. In the CRF group, there were significant increases in tissue MDA and PC levels in all tissues with marked reductions in GSH levels compared with controls (P < 0.05-0.001). In the plasma, while MDA and PC levels increased, GSH, SOD, CAT, and GSH-Px activities were reduced. Melatonin treatment reversed these effects as well. In this study, the increase in MDA and PC levels and the concomitant decrease in GSH levels of tissues and plasma and also SOD, CAT, GSH-Px activities of plasma demonstrate the role of oxidative mechanisms in CRF-induced tissue damage, and melatonin, via its free radical scavenging and antioxidant properties, ameliorates oxidative organ injury. CRF-induced dysfunction of the aorta and corpus cavernosum of rats was reversed by melatonin treatment. Thus, supplementing CRF patients with adjuvant therapy of melatonin may have some benefit.     

脑型疟发病中肿瘤坏死因子α与一氧化氮的作用机制研究

目的 研究肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)与一氧化氮(nitric oxide,NO)在脑型疟(cerebral malaria,CM)发病中的作用. 方法首先建市C57BL/6J小鼠的CM动物模型.然后,取雌性(C57BL/6J 小鼠100只,随机分为:正常对照组,腹腔注射生理盐水;感染对照组,接种约氏疟原虫By265;CM模型组,腹腔注射感染们氏疟原虫K173;地塞米松处理组,于感染伯氏疟原虫K173前一天在饮水中加入地塞米松,浓度为10 ms/L;L-硝基精氰酸(L-NNA)处理组,从感染伯氏疟原虫K173当天开始每只每大腹腔注射25 g/L的L-NNA溶液0.2 ml.每组均为20只.CM 模型组鼠于CM发病时取脑组织,其他各组小鼠于感染后第10天取脑组织匀浆.观察脑组织TNF-α、NO及氧化氮合酶(nitric oxide synthase,NOS)在CM发病过程中的含量变化;同时观察TNF-α合成抑制剂地塞米松及NO合成抑制剂L-NNA对脑组织中TNF-α和NO浓度的影响. 结果 (1)CM模型组小鼠均发牛CM,地塞米松组、L-NNA 组及感染对照组小鼠至感染后第10天均末发生CM.(2)小鼠CM发病时脑组织TNF-α、NO、NOS均高于感染第5天(P＜0.01).(3)小鼠CM发病时和感染后第5天脑组织FNF-α、NO、NOS均高于感染对照组和止常对照组(P＜0.01).(4)地塞米松组小鼠感染后第10天、第5天与同时间CM模型组比较,脑组织TNF-α均明显下降(P＜0.01).(5)L-NNA组与CM模型组比较,脑组织NO、NOS均显著性降低(P＜0.01). 结论 (1)成功地建立起较理想的CM动物模型.(2)伯氏疟原虫感染小鼠给予地塞米松或L-NNA后,可有效地预防CM的发病.     

Mechanisms of oxidative stress-induced increase in salt sensitivity and development of hypertension in Sprague-Dawley rats

High salt intake produces vascular changes that contribute to the development of hypertension in salt-sensitive individuals. Because reactive oxygen species play a role in the pathogenesis of cardiovascular diseases, we investigated whether oxidative stress contributes to salt-sensitive hypertension. Sprague-Dawley rats were divided in different groups and received tap water (vehicle), 30 mmol/L of l-buthionine sulfoximine ([BSO] an oxidant), high salt ([HS] 1% NaCl), and BSO plus HS without and with antioxidant tempol (1 mmol/L) in drinking water for 12 days. Compared with vehicle, BSO treatment caused oxidative stress and mild increase in blood pressure. Thoracic aortic rings from BSO-treated rats exhibited decreased response to endothelium-independent vasorelaxants. In HS-treated rats, the response to vasoactive agents, as well as blood pressure, was unaffected. Concomitant treatment of rats with BSO and HS produced a marked increase in blood pressure and a decreased response to both endothelium-dependent and endothelium-independent vasorelaxants with an increase in EC(50). Incubation of aortic tissue from BSO-treated rats with sodium nitroprusside showed decreased cGMP accumulation, whereas HS rats had decreased basal NO synthase activity. Tempol decreased oxidative stress, normalized blood pressure, and restored NO signaling and responses to vasoactive compounds in BSO and BSO plus HS rats. We conclude that BSO increases oxidative stress and reduces NO signaling, whereas HS reduces NO levels by decreasing the NO synthase activity. These phenomena collectively result in reduced responsiveness to both endothelium -dependent and endothelium- independent vasorelaxants and may contribute to salt-sensitive hypertension.     

The lack of a modulating effect of non-genetic factors (age, gonads and maternal environment) on the phenotypic expression of the salt-susceptibility genes in the Sabra rat model of hypertension

OBJECTIVE: This study was designed to test the hypothesis that non-genetic factors such as age, gonads and maternal environment modulate the expression of the salt-susceptibility genes and affect the blood pressure response to salt-loading (salt-sensitivity and salt-resistance) in the Sabra rat model of hypertension. METHODS: The blood pressure response to salt-loading was studied in Sabra hypertension prone (SBH/y) and Sabra hypertension resistant (SBN/y) rats of both sexes: (1) at 1, 3, 6, 9 and 12 months of age, (2) in adult rats after orchiectomy or oophorectomy, and (3) in animals that had been raised and nourished from birth to weaning by a foster mother from the contrasting strain. In each of the study protocols, systolic blood pressure was measured at baseline by the tail cuff method, animals were salt-loaded with deoxycorticosterone acetate, and blood pressure was measured again after 4 weeks. RESULTS: Basal blood pressure at all the ages studied and in both sexes was on average 10-15 mmHg higher in SBH/y than in SBN/y. Salt-loading in SBN/y of both sexes aged 1-12 months did not induce any significant increment in blood pressure. Salt-loading in SBH/y, in contrast, caused a highly significant rise in systolic blood pressure, of 40 mmHg or more at all the ages studied. There was no age difference or sex dependence in the magnitude of the blood pressure response to salt Oophorectomy or orchiectomy did not affect the levels of basal blood pressure nor prevent the hypertensive response to salt-loading in SBH/y or the lack of a hypertensive response in SBN/y rats. Gonadectomy did not affect blood pressure in salt-loaded hypertensive SBH/y nor in salt-loaded normotensive SBN/y. The basal blood pressure and the blood pressure responses of SBH/y and SBN/y of both sexes raised by foster mothers of the contrasting strains from birth to weaning were not different from those observed when raised by their natural mothers. CONCLUSIONS: This study indicates that salt-sensitivity in SBH/y and salt-resistance in SBN/y are not age-dependent phenomena; that the magnitude of the BP response to salt-loading is not sex-dependent; and that neither gonadectomy nor the maternal environment affect the blood pressure response to salt-loading in the adult animal of either strain. These non-genetic factors thus do not modulate expression of the salt-susceptibility genes in the Sabra genetic model of salt-sensitive hypertension.     

D-半乳糖催老大鼠氧化水平和抗氧化能力的变化

目的　研究人工催老大鼠氧化水平和抗氧化能力的改变。方法　采用D 半乳糖 6 0mg/kg皮下注射 4 2d ,复制人工催老大鼠模型 ,以观察催老大鼠血中丙二醛 (MDA)、一氧化氮 (NO)的含量、超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GSH Px)、一氧化氮合酶 (NOS)和脑单胺氧化酶 (MAO)等活性的变化。结果　催老大鼠与正常大鼠相比 ,血清中MDA含量增高 ,SOD和GSH Px活性降低 ,脑MAO活性增高 ,NO含量和NOS活性无明显改变。结论　D 半乳糖可以使催老大鼠氧化水平增加 ,抗氧化能力下降 ;且两者变化无性别差异。     

不同浓度脂联素通过减轻氧化应激损伤保护缺血再灌注心肌

目的观察不同浓度脂联素对大鼠心肌缺血再灌注损伤及其所引起的氧化应激的影响,以探讨脂联素保护缺血再灌注心肌是否与减轻氧化应激有关。方法将80只健康SD大鼠随机分成假手术组、缺血再灌注组、低浓度脂联素组(60 ng/g)、中浓度脂联素组(120 ng/g)和高浓度脂联素组(180 ng/g),每组16只。假手术组只穿线,不结扎,旷置225 m in;缺血再灌注组冠状动脉前降支结扎45 m in后,再灌注180 m in;各脂联素组于缺血前30m in经股静脉给予不同浓度脂联素,再进行缺血再灌注。各组进一步随机分为两个亚组。亚组1(8只)在缺血45m in再灌注180 m in后,用Evans b lue-TTC双染法测定心肌梗死面积;亚组2(8只)在大鼠再灌注180 m in后对左心室内压及单位时间左心室内压变化值(±dp/dt)等血流动力学指标进行检测。实验结束后,在心尖处取血并取心肌组织,测定大鼠血清超氧化物歧化酶活性、心肌组织总一氧化氮合酶及一氧化氮含量。结果与假手术组比较,缺血再灌注组大鼠血清中超氧化物歧化酶活性及心肌组织中总一氧化氮合酶和一氧化氮含量明显下降,心肌梗死面积增大;与缺血再灌注组比较,各浓度脂联素组心肌梗死面积减小,心肌舒缩功能有所改善,大鼠血清超氧化物歧化酶活性及心肌组织总一氧化氮合酶和一氧化氮含量显著增加,并随脂联素浓度增加而增加。结论脂联素对缺血再灌注心肌细胞有保护作用,减少缺血再灌注心肌的梗死面积,改善心脏舒缩功能;其作用机制可能是通过增加缺血再灌注心肌组织总一氧化氮合酶和一氧化氮含量及血清超氧化物歧化酶活性,从而减轻氧化应激损伤。     

Effect of a high salt diet on microvascular antioxidant enzymes

High dietary salt intake decreases the endothelium-dependent dilation of skeletal muscle arterioles by inhibiting local nitric oxide (NO) activity without changing vascular smooth muscle responsiveness to NO. Under these conditions, microvascular walls show evidence of oxidative stress, and scavengers of reactive oxygen species (ROS) abolish this oxidative stress and restore normal arteriolar responses to acetylcholine (ACh). We tested the hypothesis that the salt-dependent appearance of microvascular ROS, and accompanying reduction in endothelium-dependent dilation, is due to a decrease in antioxidant enzyme expression or activity. We studied spinotrapezius muscle microvessels in rats fed normal (NS) (0.45%) or high (HS) (7%) salt diets for 4-5 weeks. Western analysis of arteriolar and venular protein showed no difference between groups in the content of superoxide dismutase (Cu/Zn SOD), catalase, or glutathione peroxidase. The catalase inhibitor 3-amino-1,2,4-triazole (3AT) increased arteriolar and venular oxidant activity (assessed by tetranitroblue tetrazolium reduction) by the same amount in both groups, suggesting similar levels of catalase activity. 3AT did not affect arteriolar responses to ACh in either group. The Cu/Zn SOD inhibitor diethyldithiocarbamate increased arteriolar and venular oxidant activity to a lesser extent in HS rats, suggesting reduced Cu/Zn SOD activity in this group. Cu/Zn SOD inhibition decreased arteriolar responses to ACh only in NS rats. These findings suggest that endogenous Cu/Zn SOD preserves the endothelium-dependent control of arteriolar tone in NS rats, and that a reduction in Cu/Zn SOD activity contributes to the loss of arteriolar NO activity in HS rats.     

The effects of vitamin E on brain derived neurotrophic factor,tissues oxidative damage and learning and memory of juvenile hypothyroid rats

The effects of vitamin E (Vit E) on brain derived neurotrophic factor (BDNF) and brain tissues oxidative damage as well as on learning and memory impairments in juvenile hypothyroid rats were examined. The rats were grouped as: (1) Control; (2) Propylthiouracil (PTU); (3) PTU-Vit E and (4) Vit E. PTU was added to their drinking water (0.05%) during 6 weeks. Vit E (20 mg/kg) was daily injected (IP). Morris water maze (MWM) and passive avoidance (PA) were carried out. The animals were deeply anesthetized and the brain tissues were removed for biochemical measurements. PTU increased the escape latency and traveled path in MWM (P?<?0.001). It also shortened the latency to enter the dark compartment of PA as well as the time spent in the target quadrant in probe trial of MWM (P?<?0.01-P?<?0.001). All the effects of PTU were reversed by Vit E (P?<?0.01-P?<?0.001). PTU administration attenuated thiol and BDNF content as well as the activities of superoxide dismutase (SOD) and catalase (CAT) in the brain tissues while increased molondialdehyde (MDA). Moreover, Vit E improved BDNF, thiol, SOD and CAT while diminished MDA. The results of the present study showed that Vit E improved BDNF and prevented from brain tissues oxidative damage as well as learning and memory impairments in juvenile hypothyroid rats.     

人工致衰老和自然衰老小鼠抗氧化能力改变的对比研究

目的 对比研究人工致衰老和自然衰老小鼠氧化水平和抗氧化能力的改变。方法 20只2月龄雄性小鼠，随机分为致衰老模型组和正常对照组；致衰老模型组每日皮下注射D-半乳糖100mg／kg，正常对照组每日皮下注射等量生理盐水，持续42d;自然衰老组为15月龄同种系雄性小鼠。以丙二醛(MDA)、一氧化氮(NO)含量以及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH—Px)和一氧化氨合酶(NOS)活性等为指标，对比研究人工致衰老和自然衰老小鼠氧化水平和抗氧化能力的改变。结果 与正常对照组相比，D-半乳糖致衰老和自然衰老组小鼠血清、心、脑、肝、肺、肾等组织的MDA含量增加。血清GSH—Px活性以及血清、脑、肝、肺、肾等脏器的SOD活性降低;自然衰老组小鼠血清NO含量、NOS活性以及心脏SOD活性降低，而致衰老组血清NO含量以及NOS和心脏SOD活性无明显变化。结论 D-半乳糖致衰老小鼠氧化水平增加，抗氧化能力下降；但与自然衰老小鼠相比，仍存在一定差异。