氧化应激与血管内皮功能异常

氧化应激和人体内抗氧化系统功能处于动态平衡之中,如果抗氧化系统不能消除氧化应激,就会产生氧化损伤,导致内皮功能障碍.本文综述氧化应激的产生及其在内皮功能异常中的作用、抗氧化治疗的措施及可能机制.     

氧化应激与血管内皮功能异常

氧化应激和人体内抗氧化系统功能处于动态平衡之中,如果抗氧化系统不能消除氧化应激,就会产生氧化损伤,导致内皮功能障碍。本文综述氧化应激的产生及其在内皮功能异常中的作用、抗氧化治疗的措施及可能机制。     

硝苯地平联合有氧运动对老年原发性高血压患者血管内皮因子的影响

目的探讨硝苯地平联合有氧运动治疗老年原发性高血压患者的临床疗效及对血管内皮因子的影响。方法老年原发性高血压患者60例随机分成联合组和对照组,联合组给予硝苯地平,并配合有氧运动治疗,对照组只给予硝苯地平治疗,观察两组治疗前后血压、心率及血浆一氧化氮(NO)、内皮素(ET)-1、血管紧张素(Ang)Ⅱ含量的变化。结果联合组治疗前后血压、心率变化明显高于对照组(P<0.05);联合组血浆NO含量增加程度明显大于对照组(P<0.05);联合组血ET-1、AngⅡ含量下降程度均明显大于对照组(P<0.05)。结论硝苯地平联合有氧运动对原发性高血压具有较好的控制作用。     

有氧运动对自发性高血压大鼠骨骼肌毛细血管稀疏的影响

目的探讨有氧运动对于自发性高血压大鼠(SHR)毛细血管稀疏是否有改善作用以及其作用机制是否与血管内皮生长因子(VEGF)的表达改变有关。方法 3月龄雄性WKY和SHR随机分为WKY安静组(WKYSED)、WKY运动组(WKY-EX)、SHR安静组(SHR-SED)、SHR运动组(SHR-EX),每组各12只。WKY-SED组和SHR-SED组不进行运动干预,WKY-EX组和SHR-EX组进行12周跑台运动(20 m/min,60 min/d,5 d/w,坡度为0,相当于55%~65%VO2max)。Western blot测定VEGF蛋白在大鼠腓肠肌中的表达,免疫组织化学观测VEGF在大鼠腓肠肌中的分布变化,HE染色观察各组大鼠腓肠肌石蜡切片中毛细血管的数量。结果免疫组织化学检测结果表明SHR-SED组VEGF在大鼠腓肠肌中的分布显著低于WKY-SED组(P0.01),12周有氧运动后,SHR-EX组VEGF在大鼠腓肠肌中的分布显著高于SHR-SED组(P0.01)。Western blot结果发现SHR-SED组的VEGF表达量与WKY-SED组差异不显著(P0.05),12周有氧运动后,SHR-EX组的VEGF表达量显著高于SHR-SED组(P0.05)。HE染色结果发现SHR-SED组的毛细血管与肌纤维数比值(C/F)显著低于WKY-SED组(P0.01),12周有氧运动之后,SHR-EX组的C/F值显著高于SHR-SED组(P0.01)。结论:微血管稀疏是导致高血压的原因之一,有氧运动可以促进VEGF的表达并且促进毛细血管新生。     

叶酸干预对老年高血压患者血管内皮功能的影响

目的探讨叶酸对老年高血压患者血管内皮功能的影响。方法42例轻、中度老年高血压患者,随机分为叶酸干预组22例,对照组20例。采用高分辨率超声检测治疗前及治疗12周后肱动脉血流介导的血管内皮依赖性舒张功能与硝酸甘油介导的非内皮依赖性舒张功能。结果治疗前后两组间及组内肱动脉基础内径差异无统计学意义,叶酸干预治疗12周后与治疗前和对照组比较肱动脉血流介导的血管内皮依赖性舒张功能(11.59%±4.79%比7.15%±3.20%和8.14%±3.01%)、肱动脉硝酸甘油介导的非内皮依赖性舒张功能(19.73%±5.80%比16.69%±4.75%和17.55%±6.05%)均有明显改善(P<0.05)。结论叶酸对老年高血压患者血管内皮功能损害有一定的改善作用。     

叶酸对老年高血压患者血浆Hcy及血管内皮功能的影响

将50例轻、中度老年高血压患者随机分为观察组（降压药＋叶酸治疗）及对照组（降压药治疗）,分别采用免疫荧光法、亚硝酸盐法及放免法测定血浆同型半胱氨酸（Hcy）、NO及内皮素1（ET-1）的水平。结果与治疗前及对照组比较,观察组治疗12周后,Hcy、ET-1下降,NO升高（P均〈0．01）;Hcy与ET-1呈正相关,与NO呈负相关（r=0．6518、-0．6090,P均〈0．05）。提示叶酸可能是通过降低Hcy而改善老年高血压患者的血管内皮功能。     

氧化应激与高血压血管损伤

氧化应激是体内活性氧介质（ROS）活性过强的一种状态，与高血压等血管性疾病密切相关。本文综述了ROS生成增多介导高血压血管损伤方面的研究进展，包括酪氨酸激酶氧化还原活性的认识，人血管壁内生成ROS的酶及其与动脉粥样硬化、高血压血管损伤的关系，以及如何减轻血管氧化应激反应等。     

幼龄自发性高血压大鼠血管内皮功能研究

目的　本研究选取幼龄自发性高血压大鼠(SHR)作为研究对象 ,观察其尚未出现高血压时血浆一氧化氮 (NO)、血管壁一氧化氮合酶 (NOS)的情况及负荷运动对它的影响 ,从而进一步了解内皮功能在遗传性高血压发病中的地位。方法　 5～ 6wSHR、WKY各 2 8只随机分为静态组、运动组 ,静态组行有创血压测定、血浆NO及血管壁NOS测定 ,运动组行游泳负荷运动后行上述指标测定 ,分别比较静态组WKY、SHR 6min内的平均血压、峰血压、达峰时间、血浆NO的均数和运动组WHY、SHR的上述指标的均数 ,比较各组NOS免疫组化染色。结果　 (1)静态组WKY、SHR6min内的平均血压、峰血压、达峰时间有显著差异 (P <0 0 5 ) ;运动组WKY、SHR的平均血压、峰血压、达峰时间没有显著差异 (P >0 .0 5 ) ;(2 )静态组WKY、SHR的血浆NO无显著差异 (P <0 .0 5 ) ,运动组WKY、SHR的NO有显著差异(P <0 .0 5 ) ;无论是SHR还是SKY ,其运动组血浆NO均高于静态组 ,但WKY鼠运动组比静态组增高更明显 ;(3)各组血管壁NOS免疫组化染色范围未见明显不同。结论　SHR在高血压期前已存在内皮舒血管储备功能的不足。推测内皮舒血管功能的障碍可能参与了遗传性高血压的发病。     

高血压合并2型糖尿病患者动脉弹性与氧化应激和血管内皮功能的相关性

目的 研究高血压合并糖尿病患者肱-踝脉搏波传导速度与血清中丙二醛、超氧化物歧化酶和一氧化氮的相关性,探讨氧化应激、血管内皮功能变化在动脉硬化过程中的作用.方法 研究对象168例分为正常对照组(n=40)、原发性高血压组(n=70)和高血压合并2型糖尿病组(n=58),各组分别用比色法检测血清丙二醛、超氧化物歧化酶和一氧化氮含量,应用动脉硬化自动检测仪测定肱-踝脉搏波传导速度.结果 与对照组比较,原发性高血压组和高血压合并2型糖尿病组中丙二醛水平和肱.踝脉搏波传导速度明显增高(P<0.01),超氧化物歧化酶和一氧化氮水平明显降低(P<0.01);与原发性高血压组比较,高血压合并2型糖尿病组丙二醛水平和肱-踝脉搏波传导速度明显增高(P<0.05),超氧化物歧化酶和一氧化氮水平降低(P<0.05).相关分析显示肱-踝脉搏波传导速度与年龄、收缩压、舒张压、胆固醇、空腹血糖、高敏C反应蛋白和丙二醛呈正相关(相关系数r分别为0.418、0.672、0.469、0.179、0.392、0.277和0.571,均P<0.05),与超氧化物歧化酶和一氧化氮呈负相关(r分别为-0.438和-0.571,均P<0.05).多元逐步回归分析显示收缩压、丙二醛、空腹血糖和年龄是肱-踝脉搏波传导速度的独立危险因素.结论 高血压合并糖尿病患者动脉弹性明显减弱,且与体内氧化应激增强和血管内皮功能损伤有关,提示氧化应激和血管内皮功能在动脉硬化过程中起重要作用.     

老年冠心病合并高血压患者血管内皮功能的改变

目的 探讨老年冠心病合并高血压患者血管内皮功能的改变。方法 将90例冠心病患者分组：52例为合并高血压病组，其中老年组（A组）35例及非老年组（B组）17例；38例为非高血压组，其中老年组（C组）25例及非老年组（D组）13例。测定血总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL）、低密度脂蛋白（LDL）、一氧化氮（NO）、内皮素（ET）等，测肱动脉血压SBP、DBP，采用高分辨超声检测肱动脉基础动脉内径（D0）、内皮依赖性血流介导的舒张功能（FMD）、非内皮依赖性硝酸甘油介导的舒张功能（NID）。结果 A组与B组、C组与D组、A组与C组、B组与D组的FMD、ET、NO有显著性差异（P〈0．01～P〈0．05）。各组D0、NID无显著性差异（P〉0．05）。FMD与NO呈正相关（P〈0．01）；FMD与ET、SBP、DBP、TC、LDL呈负相关（P〈0．01）；SBP、DBP与ET呈正相关（P〈0．01）；SBP、DBP与NO呈负相关（P〈0．01）。结论 老年冠心病患者存在显著的内皮功能障碍，高血压加重冠心病患者的内皮功能障碍，FMD与NO、ET可作为反映冠心病和高血压者血管内皮功能的无创指标。     

Potential ergogenic effects of L-arginine against oxidative and inflammatory stress induced by acute exercise in aging rats

In this study, we report protective effects of dietary L-arginine (L-Arg) supplementation against oxidative stress and inflammation in aging rats during exhaustive exercise. Thirty 18-month-old male Sprague-Dawley rats were randomly divided into four groups: sedentary control (SC); sedentary control with L-Arg treatment (SC+Arg); exhaustive exercise (E); and exhaustive exercise with L-Arg treatment (E+Arg). Rats in groups SC+Arg and E+Arg received a 2% L-Arg diet. Rats in groups E and E+Arg performed an exhaustive running test on a treadmill. The mean duration of exercise differed significantly between groups E and E+Arg (51+/-6 versus 63+/-3min). Results showed significant increases in xanthine oxidase (XO) and myeloperoxidase (MPO) activities and in lipid peroxidation end-product (malondialdehyde, MDA) levels of myocardial, muscular, hepatic, pulmonary, and renal tissues of exercised rats compared with SC and SC+Arg rats. The increased XO and MPO activities and MDA levels significantly decreased in exercised rats that were fed a diet supplemented with L-Arg. We also found that L-Arg supplementation prevented exhaustive exercise-induced elevations of plasma aminotransferase activity, and lactate and uric acid levels in aging rats. These findings suggest that L-Arg supplementation enhances exercise capacity and protects against oxidative damage and inflammatory responses caused by exhaustive exercise in aging rats.     

苯那普利对老年高血压病患者血管内皮功能的影响

目的　探讨苯那普利对老年高血压血管内皮功能的影响。方法　采用放射免疫法测定 32例老年高血压患者服用苯那普利前后血管内皮功能的影响变化。结果　治疗前 ET水平升高 ,NO水平降低 ,与对照相比有显著性差异 (P<0 .0 1 )。治疗后 ET水平降低 ,NO水平升高 ,治疗前后比较有显著的差异性。结论　苯那普利可降低 ET,升高 NO,从而改善血管内皮功能。     

Blood pressure and autonomic responses following isolated and combined aerobic and resistance exercise in hypertensive older women

Purpose: This study aimed to compare blood pressure (BP) after isolated and combined sessions of aerobic and resistance exercises in hypertensive older women. Heart rate (HR) and heart rate variability (HRV) were included as additional variables. Methods: Twenty-one older women (63±1.9 years; 69.9±2.7 kg; 158.8±2.1 cm) with controlled hypertension (resting BP = 132.2 ± 3.1/74.1 ± 4.0 mmHg) performed four random sessions on different days: 1) aerobic exercise (AE: treadmill walking/running; 40 min; 50–60% HR_reserve); 2) resistance exercise (RE: 8 exercises; 3 sets; 15 reps; 40% 1RM)); 3) aerobic exercise followed by resistance exercise (A+R); 4); control (CON). BP, HR and HRV were measured at rest and during 180 min after the sessions. Results: The AE and A+R sessions demonstrated significant decreases in SBP and DBP (30, 60, 120, and 180 min; P < 0.05) and increases in HR (30 and 60 min; P < 0.05) compared to the CON. The RE session demonstrated significant reductions compared to the CON only for DBP (120 and 180 min; P < 0.05). No significant differences were observed in HRV between resting and all sessions. Conclusion: All sessions that involved aerobic exercise (AE and A+R) caused postexercise hypotension in comparison to the CON, with no differences in HRV.     

Oxidative stress in hypertensive,diabetic, and diabetic hypertensive rats

BACKGROUND: Reactive oxygen species play a key role in the formation of endothelial dysfunction accompanying diabetes mellitus, hypertension, and other cardiovascular diseases. METHOD: This study compares oxidative stress (OS) in Wistar-Kyoto rats (WKY), spontaneously hypertensive rats (SHR), non-insulin-dependent Cohen Diabetic rats (CDR), and Cohen Rosenthal diabetic hypertensive rats (CRDH), a unique animal model of both diabetes and hypertension. The OS was evaluated with a newly developed thermochemiluminiscence (TCL) analyzer (Lumitest Ltd., Nesher, Israel) that measures the oxidizability (ie, susceptibility to oxidation) of a test sample. RESULTS: The TCL oxidizability test results of sera from the different rats groups showed a time-dependent increase in TCL of up to 145% +/- 7% for WKY, 160% +/- 8% for SHR, 179% +/- 12% for CDR, and 226% +/- 15% for CRDH. These results were significant: P <.001 for SHR and CDR and P <.0001 for CRDH in comparison to WKY. Lipid peroxide levels also increased in each strain of rats: to 80 +/- 7.8 nmol/mL in WKY, 104 +/- 10.1 nmol/mL in SHR, 110 +/- 9.4 nmol/mL in CDR, and 167 +/- 11.7 nmol/mL in CRDH. These results were also significant: P <.001 for SHR, CDR and CRDH in comparison to WKY. CONCLUSION: The combination of hypertension and diabetes is accompanied by higher oxidative stress than that seen with either disorder alone.     

The immediate effect of aerobic exercise on haemostatic parameters in patients with recently diagnosed mild to moderate essential hypertension

Background Exercise is frequently recommended for the treatment of patients with arterial hypertension. Previous studies have shown an enhanced coagulation state after exercise. Our study investigates the alterations observed after a single session of submaximal aerobic exercise concerning coagulation, fibrinolysis, platelet activation as well as endothelial function in patients with recently diagnosed essential hypertension. Methods Twenty non-diabetic patients with recently diagnosed essential hypertension participated in a 45 min submaximal exercise test on a bicycle ergometer. Blood samples were drawn before and after exercise in order to determine parameters of coagulation activation (Prothrombin time [PT], activated Partial Thromboplastin time [aPTT], fibrinogen, D-Dimers, prothrombin fragments 1 + 2 [PF1+2], thrombin-antithrombin III complex [TAT] and factors VII, VIII and XII), platelet activation (Platelet count, Platelet factor 4 [PF4] and β-thromboglobulin [β-TG]), fibrinolysis activation (Plasmin-a₂ antiplasmin complex, PAP) and endothelial function (soluble Thrombomodulin [sTM] and von Willebrand factor [vWf]). Soluble P-selectin served as a marker for endothelial and platelet activation. Results All patients completed the exercise test. aPTT (P < 0.001) and factor VII (P = 0.01) significantly decreased while PT (P = 0.04), fibrinogen (P = 0.008), factor VIII (P < 0.001), platelet count (P = 0.002) and β-TG levels (P = 0.01) significantly increased as a result of exercise. Compared to baseline there was an 11% increase in TAT (P = 0.04) and a 28% increase in PAP (P < 0.001) at peak exercise. One hour post exercise, there was a 43% increase in PAP whereas TAT levels became similar to those at baseline. Additionally vWf (P = 0.01) and sP-selectin (P = 0.02) levels significantly increased throughout the exercise protocol. Conclusions Patients with recently diagnosed and never treated mild to moderate essential hypertension undergoing submaximal aerobic exercise present evidence of enhanced fibrinolysis compared with a mild increase of coagulation indices. However, whether there is a favourable effect of exercise on fibrinolysis over coagulation and/or endothelial involvement during exercise needs to be further investigated.     

有氧踏车运动对老年单纯收缩期高血压患者大动脉弹性的影响杨志伟 徐佳 董波 曾令忠 沈丹萍作者单位：湖南省老年医院 心血管内科 410016

目的 探讨有氧踏车运动对老年单纯收缩期高血压（ISH）患者大动脉弹性的影响.方法 选取2012年1～12月期间我院收治的老年ISH患者102例,随机分为2组.A组（52例）给予常规治疗;B组（50例）在常规治疗基础上进行有氧踏车运动,每周3次,每次30 min.疗程均为20周.检测试验前后收缩压、舒张压、高敏C反应蛋白（hs-CRP）、低密度脂蛋白（LDL）和脉搏波传导速度（baPWV）.结果 20周干预后,与治疗前比较,两组收缩压[（145.76±11.52）mm Hg比（165.54±13.87）mm Hg,（141.16±7.69）mm Hg比（162.81±13.26）mm Hg]、舒张压[（65.87±7.20）mm Hg比（72.71±8.16）mm Hg,（67.98±8.21）mm Hg比（71.48±9.18）mmHg]均明显下降,baPWV[（1641.46±119.38）mm/s比（1690.71±124.65）mm/s,（1593.76±112.21）mm/s比（1671.48±138.72）mm/s]减慢,P均＜0.05.与A组对比,B组的收缩压[（141.16±7.69）mm Hg比（145.76±11.52）mmHg]、baPWV[（1593.76±112.21）mm/s比（1641.46±119.38）mm/s]下降更明显,P均＜0.05.结论 有氧踏车运动能够改善老年ISH患者的动脉僵硬度,并有助于其血压的降低.     

Acute blood pressure response in hypertensive elderly women immediately after water aerobics exercise: A crossover study

Water aerobics exercise is widely recommended for elderly people. However, little is known about the acute effects on hemodynamic variables. Thus, we assessed the effects of a water aerobic session on blood pressure in hypertensive elderly women. Fifty hypertensive elderly women aged 67.8 ± 4.1 years, 1.5 ± 0.6 m high and BMI 28.6 ± 3.9 kg/m², participated in a crossover clinical trial. The experiment consisted of a 45-minute water aerobics session (70%–75% HRmax adjusted for the aquatic environment) (ES) and a control session (no exercise for 45 minutes) (CS). Heart rate was monitored using a heart rate monitor and systolic blood pressure (SBP) and diastolic (DBP) measurements were taken using a semi-automatic monitor before and immediately after the sessions, and at 10, 20 and 30 minutes thereafter. It was using a generalized estimating equation (GEE) with Bonferroni’s post-hoc test (p < 0.05). At the end of the experimental session, ES showed a rise in SBP of 17.4 mmHg (14.3%, p < 0.001) and DBP of 5.4 mmHg (7.8%, p < 0.001) compared to CS. At 10 minutes after exercise, BP declined in ES by a greater magnitude than in CS (SBP 7.5 mmHg, 6.2%, p = 0.005 and DBP 3.8 mmHg, 5.5%, p = 0.013). At 20 minutes after exercise and thereafter, SBP and DBP were similar in both ES and CS. In conclusion, BP returned to control levels within 10–20 minutes remaining unchanged until 30 minutes after exercise, and post-exercise hypotension was not observed. Besides, BP changed after exercise was a safe rise of small magnitude for hypertensive people.     

全反式维甲酸对高血压大鼠心脏氧化应激水平的影响

目的:探讨全反式维甲酸(atRA)对高血压心脏还原型辅酶I氧化酶P22亚单位(p22phox)表达以及氧化应激水平的影响。方法:采用12周龄雄性自发性高血压大鼠(SHR)及其同源对照WKY大鼠,经腹腔注射at-RA,为期1月。分别采用免疫印迹、硫代巴比妥酸比色以及透射电镜技术测定atRA治疗后SHR心脏p22phox的表达、丙二醛(MDA)含量以及心肌超微结构情况。结果:与WKY对照组相比,SHR心脏组织中p22phox蛋白表达与MDA含量明显升高(P均<0.01)。而atRA治疗后SHR(低、高剂量atRA组)大鼠心脏组织中p22phox蛋白表达与MDA水平出现下调(P均<0.05),同时伴有心肌损伤减轻。结论:长期atRA治疗可降低SHR大鼠心脏组织中p22phox表达与MDA水平,提示atRA在高血压病中具有一定的抗氧化效应。     

普伐他汀改善老年陈旧性心肌梗死患者血管内皮功能的研究

目的 :研究普伐他汀对老年陈旧性心肌梗死 (OMI)患者血管内皮的作用并初步探讨其可能机制。方法 :将 6 0例老年OMI患者随机均分为安慰剂 (C)组和普伐他汀 (P)组 ,分别测定血脂 [总胆固醇 (TC)、三酰甘油 (TG)、低密度脂蛋白胆固醇 (LDL C)、高密度脂蛋白胆固醇 (HDL C) ]、血浆内皮素 (ET)及一氧化氮 (NO)浓度变化 ,血小板表面α颗粒膜蛋白 (GMP 14 0 )表达及内皮依赖性扩张百分率 (FMD % )和非内皮依赖性扩张百分率(GTN % )。结果 :P组经普伐他汀治疗 6周后 ,TC含量较治疗前下降 2 9% ,LDL C下降 35 % ,HDL C升高 8% ,但TG水平无明显变化 ,内皮功能得到了明显的改善 ,GMP 14 0表达受到抑制 ,而这种表达抑制与血胆固醇水平的改变无关。结论 :普伐他汀能通过调脂及抑制血小板的活性参与血管内皮功能的改善 ,在老年OMI患者中应用普伐他汀可能通过改善内皮功能达到降低心脑血管事件发生的目的