有氧运动对衰老大鼠骨骼肌抗氧化能力的影响

目的 研究有氧运动对衰老大鼠股四头肌组织中抗氧化酶和过氧化脂质的影响.方法 建立衰老大鼠模型,随机分为对照组和运动组,运动组分别给予每天0.5、1、2 h游泳训练,12 w后检测骨骼肌组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、过氧化氢酶(CAT)、丙二醛(MDA)、H2O2含量.结果 有氧运动训练可以引起衰老大鼠股四头肌SOD、GSH-Px和CAT活性的升高,以1 h运动组效果最优,并且有效地减少MDA含量.结论 长期规律的有氧运动可以提高骨骼肌的抗氧化能力,有效地减少MDA含量,降低脂质过氧化水平,并且在适宜的运动负荷之内,随着时间的延长其减少氧自由基损害作用越大.     

有氧运动抑制老年高血压大鼠血管功能重塑的氧化应激机制

目的研究有氧运动对老年自发性高血压大鼠(SHR)内皮功能的影响,探讨氧化应激在其中的作用机制。方法实验选用24只16月龄雄性SHR大鼠,随机分为高血压安静组(SHR-C,n=12)、高血压运动组(SHREX,n=12);选用24只同龄雄性正常血压大鼠(WKY),随机分为正常血压安静组(WKY-C,n=12)、正常血压运动组(WKY-EX,n=12)。运动组以16~18 m/min进行8周跑台运动(0°slope,5 d/w,60 min/d),安静组不进行任何运动干预。8周训练末进行血压测定、离体肠系膜动脉张力测定、氧化应激相关指标和一氧化氮(NO)含量检测。结果SHR-EX组收缩压显著低于SHR-C组(P0.05),而WKY-EX组收缩压与WKY-C组无显著性差异(P0.05)。SHR-C组血清丙二醛(MDA)含量(11.8±1.0μmol/L)显著高于WKY-C组(7.2±0.3μmol/L,P0.05),而SHR-EX组血清丙二醛(MDA)含量(7.9±0.3μmol/L)显著低于SHR-C组(P0.05);各组间主要的抗氧化物酶谷胱甘肽过氧化物酶和过氧化物歧化酶没有显著差异(P0.05)。SHR-C组NE诱发的血管收缩反应(153.2±1.9%KMAX)显著高于WKY-C组(120.2±5.6%KMAX,P0.05),SHR-EX组NE诱发的血管收缩反应(136.0±1.8%KMAX)显著低于SHRC组(P0.05),但WKY-EX组NE诱发的血管收缩反应(143.9±4.3%KMAX)仍显著高于WKY-C组(P0.05);SHRC组内皮依赖性血管舒张(50.2±2.8%NE)显著小于WKY-C组(100.1±0.6%NE,P0.05),SHR-EX组内皮依赖性血管舒张(97.0±1.5%NE)显著高于SHR-C组(P0.05)。离体微血管环加入NADPH氧化酶抑制剂Apocynin预孵育15 min后,SHR-C组血管内皮最大舒张(98.6±1.3%NE)显著增高(P0.05)。SHR-C组NO依赖性血管舒张(25.5%±2.3%)显著低于WKY-C组(85.2%±0.7%,P0.01),SHR-EX组和WKY-EX组NO依赖性血管舒张(86.8%±3.4%和98.8%±1.5%)显著高于对应的安静组(P0.05)。结论长期有氧运动抑制由衰老和/或高血压诱导的氧化应激水平增高、NO生物利用度降低,进而改善血管内皮功能障碍。     

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。     

血管内皮生长因子与自发性高血压大鼠血管重构的关系

目的探讨血管内皮生长因子与血管重构的关系。方法12只13周龄雄性自发性高血压大鼠(SHR组)作为观察组,12只同周龄雄性WKY大鼠作为正常血压对照组(WKY组)。分别于实验的第4、8周末每组处死大鼠各6只。采用酶联免疫吸附法测定血浆血管内皮生长因子浓度;放射免疫法测定颈动脉血管紧张素Ⅱ浓度;病理图象管理系统测定颈动脉管腔横截面积、内弹力层围绕面积、外弹力层围绕面积,评价内膜和中膜增生程度;免疫组织化学法检测颈动脉血管内皮生长因子蛋白表达。结果与WKY组比较,SHR组血浆血管内皮生长因子浓度明显下降,颈动脉血管内皮生长因子蛋白表达明显减弱,颈动脉血管紧张素Ⅱ浓度却显著升高(P<0.01),8周末这一作用更加显著(P<0.01);SHR组内膜增生较WKY组明显,中膜面积显著增大(P<0.01)。结论在血管重构过程中,血管内皮生长因子水平下降,提示血管内皮生长因子可能具有改善血管重构的作用。     

有氧运动对自发性高血压大鼠心脏炎症的影响及机制的探讨

目的 探讨有氧运动对自发性高血压大鼠（SHR）心脏炎症的调节及其机制。方法 8周龄雄性SHR大鼠和正常血压对照WKY大鼠各16只,将SHR大鼠随机分为SHR安静组和SHR运动组;将WKY大鼠随机分为WKY安静组和WKY运动组,每组8只。其中运动组大鼠进行8周无负重游泳运动。采用超声心动仪检测心脏功能,用ELISA试剂盒检测心脏炎症因子TNF-α和IL-1β的含量,Western blot法检测心脏叉头框蛋白1（FoxO1）、p65 NF-κB、磷酸化Akt（p-Akt）和总Akt（t-Akt）的表达。结果 与WKY安静组大鼠相比,SHR安静组大鼠左心室p65 NF-κB的表达以及炎症因子TNF-α、IL-1β的含量及FoxO1表达明显升高（P<0.05,P<0.01）,p-Akt的水平下降（P<0.05）;与SHR安静组相比,8周有氧运动能够增强SHR大鼠心脏功能,降低p65 NF-κB的表达以及炎症因子TNF-α和IL-1β的含量（P<0.05）,同时降低FoxO1表达（P<0.05）,提高p-Akt的水平（P<0.05）。8周有氧运动同样能够降低WKY大鼠心脏FoxO1表达（P<0.05）,提高p-Akt的水平（P<0.05）。结论 8周无负重游泳运动能够降低SHR大鼠心脏炎症因子TNF-α和IL-1β的含量,其可能与加强Akt磷酸化水平和下调FoxO1表达有关,确切机制有待进一步研究。     

VEGF在脓毒症毛细血管渗漏中的作用

脓毒症发病率高、痫死率高、治疗费用高,是危重患者主要死亡原因之一,其根本发病机制不清。近年研究表明,微血管通透性增加是脓毒症发生发展的关键因素,而血管内皮生长因子（VEGF）是控制血管通透性的关键分子,是导致炎症相关毛细血管通透性增加的潜在因素。脓毒症早期VEGF增高,致微血管通透性增加,毛细血管渗漏,加重炎症反应,脓毒症患者普遍存在毛细血管渗漏现象。VEGF是一种细胞因子,广泛存在于机体并参与体内多种疾病过程。本文对VEGF在脓毒症中的作用机制加以综述。     

有氧运动对轻中度原发性高血压患者血压的影响

目的探讨有氧运动对轻中度原发性高血压患者血压的影响。方法选择2010年10月—2011年12月我院收治的轻中度原发性高血压患者20例,均进行12周的有氧运动,观察有氧运动前后患者血压、睡眠不足所占比例及焦虑自评量表(SAS)评分的变化。结果有氧运动12周后,患者收缩压为(138±7)mm Hg,舒张压为(83±7)mm Hg,低于有氧运动前的(149±8)mm Hg、(95±7)mm Hg(P0.05);治疗后睡眠不足者所占比例和SAS评分均低于治疗前(P0.05)。结论有氧运动对轻中度原发性高血压患者血压具有调节作用,且能改善患者生活质量,可以作为部分轻中度原发性高血压患者尤其是早期患者单独选用的干预方法。     

低氧反应元件对大鼠骨骼肌成肌细胞转染表达血管内皮生长因子基因的调控作用

目的:研究低氧反应元件(HRE)对血管内皮生长因子(VEGF)基因121在原代培养大鼠骨骼肌成肌细胞中转染表达的调控作用。方法:利用分子生物学方法,构建pEGFP-C3-9HRE-CMV-VEGF121载体,通过脂质体介导将其转染到原代培养的大鼠骨骼肌成肌细胞中。在不同低氧浓度及不同缺氧时间下培养,通过RT-PCR、Western-Blot及荧光显微镜检测转基因成肌细胞的基因表达情况。结果:低氧浓度组可见明显目的基因条带,且随着氧浓度的降低及缺氧时间的延长,目的基因表达增强;低氧环境下,转染后的成肌细胞表达VEGF121蛋白产物明显增加;低氧环境下可见报告基因EGFP表达,常氧环境下未见报告基因表达。结论:以多拷贝HRE构建低氧启动子插入VEGF基因上游,可作为控制VEGF基因表达的开关,这对于防止VEGF基因转染的成肌细胞移植后VEGF基因过度表达所引起的安全问题,提高基因治疗的安全性有重要意义。     

间歇有氧运动上调自发性高血压大鼠血管肾上腺髓质素

目的研究间歇有氧运动(IAE)对自发性高血压大鼠(SHR)主动脉肾上腺髓质素(ADM)的影响,探讨运动降低血压的大血管因素及其机制。方法 SHR 30只,随机分为间歇有氧运动组(IAE组)和对照组。IAE组进行8周间歇跑台有氧运动。采用尾压法测血压,酶联免疫吸附法(ELISA)测运动前后血清中ADM的含量,免疫组织化学法显示SHR主动脉ADM的表达,蛋白质印迹实验检测主动脉ADM的特异性受体——受体活性修饰蛋白2(RAMP2)和降钙素受体样受体(CRLR)定量水平。结果 IAE组血压明显低于对照组(P0.05);IAE组血清中ADM的含量明显高于对照组(P0.05);主动脉ADM表达明显强于对照组(P0.05);主动脉RAMP2和CRLR定量均明显高于对照组(P0.05)。结论间歇有氧运动可能通过增强血管ADM及其特异性受体表达使SHR大鼠血压下降。     

糖尿病模型大鼠骨骼肌VEGF、bFGF、NGF的表达及意义

目的 探讨骨骼肌血管内皮生长因子(VEGF)、碱性成纤维细胞生长因子(bFGF)、神经生长因子(NGF)与糖尿病肌病发生的关系.方法 选用 SD 大鼠,随机分成对照组和模型组.以链脲佐菌素 50 mg/kg 腹腔注射制造糖尿病模型.8 w后观察大鼠骨骼肌病理形态学改变,同时采用免疫组化方法检测骨骼肌 VEGF、bFGF、NGF蛋白表达情况.结果 模型组大鼠骨骼肌表现为普遍性肌萎缩,肌纤维变性坏死;VEGF、bFGF、NGF在模型组大鼠骨骼肌中的表达明显减少.结论 VEGF、bFGF、NGF的表达异常参与了糖尿病肌病的发生发展.     

Angiostatin does not contribute to skeletal muscle microvascular rarefaction with low nitric oxide bioavailability

OBJECTIVE: Ischemic angiogenesis is dependent on vascular nitric oxide (NO) bioavailability, in part by reducing matrix metalloproteinases (MMP)-2 and -9 activity and angiostatin production. In the metabolic syndrome, the authors have demonstrated that reduced skeletal muscle microvessel density (SKMVD) was correlated with chronic reductions in NO bioavailability, but these relationships are complicated by the presence of the multiple pathological states inherent in the metabolic syndrome. Given this, the authors hypothesized that low NO bioavailability could reduce SKMVD in normal rats, independent of any systemic pathologies associated with the metabolic syndrome, and that this would be correlated with increased angiostatin production. METHODS: Rats were separated into 3 groups: (1) control, (2) chronic NOS inhibition (10-4 M L-NAME; drinking water), and (3) NOS inhibition/normotensive (combined L-NAME/hydralazine treatment; 50 mg/kg/d; drinking water). Vessel structure, reactivity, and NO bioavailability were assessed in isolated vessels using standard techniques. SKMVD was determined using established immunohistochemical methods. Established protein analyses were performed for MMP-2 and MMP-9 expression/activity and for angiostatin expression. Alterations in vascular endothelial growth factor (VEGF) levels under the conditions of the study were assessed using ELISA. RESULTS: After 6 weeks, MAP was elevated in L-NAME rats vs. control, although this difference was abolished in L-NAME/hydralazine rats. NOS inhibition abrogated dilation to acetylcholine and arterial eNOS activity. While NOS inhibition reduced SKMVD vs. control, hydralazine treatment did not improve density, suggesting that rarefaction in NOS-inhibited rats was independent of elevated pressure. Skeletal muscle demonstrated reduced active hyperemia and increased minimum vascular resistance in L-NAME rats, which was also associated with increased arteriolar wall stiffness. L-NAME/hydralazine treatment, while still causing an elevated resistance, prevented arteriolar wall stiffening. Protein analysis demonstrated that neither expressions nor activities of MMP-2 or MMP-9 were altered from control in skeletal muscle of rats treated with L-NAME and angiostatin production was not altered in any group. Chronic NOS inhibition was associated with no consistent change in plasma VEGF levels. CONCLUSIONS: These results suggest that a reduced SKMVD develops with low NO bioavailability, although this process was not associated with significant alterations to either VEGF or angiostatin production.     

Increased expression of vascular endothelial growth factor and capillary density in hearts of spontaneously hypertensive rats

OBJECTIVE: The role of VEGF in vascular remodeling of target organs exposed to chronic hypertension is poorly understood. The authors compared capillary density (CD), capillary-to-fiber ratio (C/F), and VEGF mRNA expression in the hearts (left ventricle [LV]), and skeletal muscles (soleus and anterior tibialis [AT]) of 18-week-old male spontaneously hypertensive rats (SHR) and age-matched male Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. METHODS: CD or C/F in LV, soleus, and AT of SHR, WKY, and SD rats was determined by analysis of randomly acquired digital images of cryosections stained with FITC-conjugated GS-I lectin. VEGF mRNA expressions in the tissues were determined by Northern blot. RESULTS: VEGF mRNA expressions in LV of SHR were 3.84- and 5.05-fold higher, compared to SD and WKY rats, respectively (n = 6; p < .01). There were no significant differences in VEGF mRNA expression in soleus or AT among SHR, WKY, and SD rats (p > .05). CD in LV of SHR (4975 +/- 167) was significantly higher than WKY or SD rats, 4151 +/- 169 and 3807 +/- 187 mm(-2), respectively (p < .05). In LV of SHR, C/F increased (35%) more significantly than CD (increased 20%), compared to WKY rats. CD, or C/F in soleus or AT of SHR was similar to that observed in WKY or 8D rats. CONCLUSIONS: VEGF expression, CD, and C/F in the heart (LV) of SHR are significantly increased, compared to WKY and SD rats. The data are consistent with the possibility that VEGF may contribute to capillary growth as a compensatory response to hypertension.     

坎地沙坦对自发性高血压大鼠骨骼肌胰岛素敏感性的影响

目的探讨血管紧张素Ⅱ(AngⅡ)受体拮抗剂(ARB)坎地沙坦对自发性高血压大鼠(SHR)骨骼肌胰岛素敏感性的影响及其机制。方法 30只SHR随机分为模型组、坎地沙坦高剂量组(Can 1组)及坎地沙坦低剂量组(Can 2组),每组10只,另选10只WKY大鼠作为对照组。均给予果糖喂养,Can 1组(0.8 mg/kg)、Can 2组(0.4mg/kg)分别给予坎地沙坦灌胃干预,观察第8周末各组大鼠胰岛素抵抗指数(HOMA-IR)和AngⅡ的水平,以及骨骼肌蛋白激酶B(Akt)的基因及蛋白表达水平。结果与对照组比较,模型组大鼠AngⅡ、HOMA-IR及血清空腹胰岛素(FINS)明显升高,骨骼肌中Akt mRNA表达及P-Akt蛋白表达显著减少,差异有统计学意义(P<0.05,P<0.01)。与模型组比较,Can 1组大鼠FINS、HOMA-IR明显降低,Can 1组和Can 2组骨骼肌Akt mRNA表达及P-Akt表达显著增加,差异有统计学意义(P<0.05,P<0.01)。结论 AngⅡ通过下调SHR骨骼肌的Akt蛋白表达引起胰岛素抵抗,而坎地沙坦通过抑制AngⅡ的这种作用改善骨骼肌胰岛素抵抗。     

Increased expression of osteoprotegerin in vascular smooth muscle cells from spontaneously hypertensive rats

Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family,whichregulates bone mass by inhibiting osteoclast differentiation and activation.Although OPG is expressed ubiquitouslyand abundantly in many tissues and cell types including vascular cells,the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) andupregulated during vascular lesion formation.Methods and Results We documented,by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats(SHR) compared to Wistar-Kyoto rats (WKY).In addition,we found that the expression of Angiotensin Ⅱ (Ang Ⅱ)type Ⅰ receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC.Furthermore,AngⅡ potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1Rsignaling pathway.Conclusions OPG expression was substantially greater in SHR VSMC,suggesting that OPGmay be an important determinant of vascular remodeling in SHR.(J Ceriatr Cardiol 2004;1:49-54.)     

有氧运动抑制高血压大鼠肠系膜动脉CaCCs通道蛋白TMEM16A表达上调

目的探究有氧运动对高血压大鼠肠系膜动脉血管钙激活氯离子通道(Ca CCs)蛋白TMEM16A的表达及血管张力的影响。方法正常血压大鼠(WKY)随机分为正常运动组(WKY-EX)和正常安静组(WKY-SED);自发性高血压大鼠(SHR)随机分为高血压运动组(SHR-EX)和高血压安静组(SHR-SED)。运动组进行12周跑台运动(20 m/min,60 min/d,5 d/w,12 w)。12周有氧运动后,取各组大鼠的肠系膜动脉(3级)进行形态学观察、离体微血管张力测定及蛋白免疫印迹分析TMEM16A蛋白。结果高血压安静组大鼠心率(HR)和收缩压(SBP)水平较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠的体质量(BW)、HR、SBP水平(P0. 05)。高血压安静组大鼠肠系膜动脉血管平滑肌层厚度较正常安静组明显增加,而12周有氧运动可下调SHR大鼠的肠系膜动脉血管平滑肌层厚度。高血压安静组大鼠肠系膜动脉对去甲肾上腺素(NE)诱导的张力反应较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对NE诱导的张力反应。高血压安静组大鼠肠系膜动脉对特异性Ca CCs蛋白阻断剂(T16Ainh-A01)的敏感性较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉对此药物的敏感性(P0. 05)。高血压安静组大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平较正常安静组显著增加(P0. 05),而12周有氧运动可显著降低SHR大鼠肠系膜动脉中Ca CCs通道蛋白TMEM16A的表达水平(P0. 05)。结论有氧运动可有效下调SHR大鼠血压,下调Ca CCs通道蛋白TMEM16A表达,抑制高血压诱导的Ca CCs通道的病理性代偿,从而引起血管功能的改善。     

Effect of aging on the structure and function of skeletal muscle microvascular networks

Humans are active creatures, yet physical activity and activity tolerance decline over the life span. One prevailing theme in the literature to account for a portion of the reduced activity tolerance with aging is the observation that the capacity to augment blood flow to skeletal muscle may be impaired with advancing age. This dysfunction may be due to adaptations in the structure or function of their microvascular networks, which collectively determine blood flow resistance. The intent of this review is to present the current knowledge of structure and function of microvascular networks from skeletal muscle with special regard to how these may adapt to, or persist through, the aging process. Skeletal muscles are supplied by an intricate branching network of arterioles and venules. The consistency of findings among available studies suggests that the overall arteriolar and venular network branching topology establishes early in development and varies little, if at all, over the life span. Microvascular networks are not a series of functionally isolated segmental branches. Rather, these networks transmit and communicate vasomotor signals along their lengths and among their branches. Current evidence suggests that aging is associated with a decrement in the capacity of upstream vessels to respond to downstream vasodilation and signals transmitted cell-to-cell along the vascular wall.     

Angiotensin receptor blockers improve insulin signaling and prevent microvascular rarefaction in the skeletal muscle of spontaneously hypertensive rats

OBJECTIVE: Spontaneously hypertensive rats are an example of an animal model of genetic hypertension with insulin resistance. The aim of this study was to investigate insulin signaling in the heart and in the skeletal muscle of spontaneously hypertensive rats, as well as to evaluate the effects of renin-angiotensin system blockade. DESIGN AND METHODS: We investigated eight untreated spontaneously hypertensive rats of 12 weeks of age and eight age-matched normotensive Wistar-Kyoto controls. In addition, eight spontaneously hypertensive rats were treated for 8 weeks with the angiotensin receptor blocker olmesartan, and eight spontaneously hypertensive rats with the angiotensin-converting enzyme inhibitor enalapril. The heart and a skeletal muscle (quadriceps femoris) were promptly dissected and frozen. Insulin signaling was evaluated by Western blot analysis of involved proteins; in addition, microvessel density was indirectly evaluated by immunohistochemistry. RESULTS: Blood pressure values were normalized by both olmesartan and enalapril. In the heart, no statistically significant difference in the expression of proteins involved in insulin signaling was observed between untreated spontaneously hypertensive rats and Wistar-Kyoto controls. On the contrary, in the skeletal muscle of untreated spontaneously hypertensive rats, we noted a significant reduction of insulin receptors, of insulin-receptor substrate-1, and of phosphorylated-mammalian target of rapamycin. The treatment with olmesartan normalized insulin signaling, including expression of glucose transporter-4, whereas the treatment with enalapril was ineffective for the insulin receptor and less effective than olmesartan on the insulin-receptor substrate-1, phosphorylated-mammalian target of rapamycin and glucose transporter-4. There was a significant reduction in microvessel density in the skeletal muscle of spontaneously hypertensive rats compared with Wistar-Kyoto controls, and this was completely prevented by both olmesartan and enalapril. CONCLUSION: These results suggest that changes in insulin signaling occur in the skeletal muscle but not in the heart of untreated spontaneously hypertensive rats. In the skeletal muscle, insulin signaling was restored by olmesartan, whereas enalapril was less effective. Effective antihypertensive treatment with olmesartan or enalapril was associated with prevention of microvascular rarefaction.     

氟伐他汀对高血压血管平滑肌细胞增殖的影响

目的：探讨氟伐他汀对自发性高血压大鼠血管平滑肌细胞增殖的抑制作用。方法：培养自发性高血压大鼠主动脉血管平滑肌细胞,不同浓度的氟伐他汀和甲羟戊干预后,进行细胞计数和＾３Ｈ－ＴｄＲ掺入率的测定。结果：（１）氟伐他汀呈浓度依赖性（１０＾－５￣１０＾－７ｍｏｌ）抑制血管平滑肌细胞数目的增加和＾３Ｈ－ＴｄＲ的掺入率;（２）１０＾－３ｍｏｌ的甲羟戊酸几科完全逆转了氟伐他汀对血管平滑肌细胞增殖的抑制作用。结论：