运动性和高血压性肥大心脏心肌内皮素及其基因表达的研究

近年来发现内皮素 (ET1)除具有强大的缩血管作用外 ,还是一个强大的致心肌肥大活性因子。为探讨(ET1)在运动性心肌肥大形成中的作用 ,本实验采用免疫组化和Northern分子杂交方法 ,对游泳运动大鼠和自发性高血压大鼠 (SHR)心肌细胞ET1分布及其基因表达进行研究。结果表明 :大鼠经 10周游泳运动后心肌细胞ET1分布和mRNA表达均比安静对照大鼠增加 ,但比安静SHR心肌细胞ET1分布和mRNA表达减少 ;SHR经 10周游泳运动后 ,心肌细胞ET1分布和mRNA表达均比安静SHR明显降低。这些结果提示 :( 1)ET1参与运动性心肌肥大形成机制 ,并在其变化特征上与高血压肥大心脏不同 ;( 2 )运动使高血压肥大心肌细胞ET1分布减少 ,在减轻ET1对肥大心脏的损伤作用方面可能具有积极意义 ;( 3 )运动可在基因转录水平上调节心肌细胞内ET1分布变化。     

心肌血管紧张素Ⅱ在运动和高血压性心肌肥大时肌球蛋白重链变化中的作用

运动和高血压心肌肥大的细胞表型改变明显不同，心肌局部血管紧张素Ⅱ（ＡｎｇⅡ）参与运动和高血压心肌肥大形成。为了解心肌局部ＡｎｇⅡ是否参与两种不同心肌肥大细胞表型变化调节，本实验对正常和自发性高血压大鼠（ＳＨＲ）运动后心肌ＡｎｇⅡ与肌球蛋白重链（ＭＨＣ）异型变化进行相关分析，结果表明正常安静大鼠心肌ＡｎｇⅡ与ａ－和β－ＭＨＣ变化无明显相关性（ｒ＝０．１７４７：０．１７３２，Ｐ＞０．０５），但经过１２周游泳训练运动后，心肌ａ－ＭＨＣ增加，ＡｎｇⅡ含量升高，两者呈正相关（ｒ＝０．７７２３，Ｐ＜０．０５）。ＳＨＲ心肌ＡｎｇⅡ和β－ＭＨＣ比ＷＫＹ高８８．０２％和４６．８９％，两者呈正相关（ｒ＝０．８７０５，Ｐ＜０．０５），ＳＨＲ心肌ＡｎｇⅡ与ａ－ＭＨＣ呈负相关（ｒ＝－０．８６２２，Ｐ＜０．０５），ＷＫＹ心肌ＡｎｇⅡ与ａ－和β－ＭＨＣ之间无明显相关性（ｒ＝０．２９３５；０．０２６３，Ｐ＞０．０５）。ＳＨＲ经１０周游泳运动后，心肌ＡｎｇⅡ含量下降，β－ＭＨＣ向ａ－ＭＨＣ逆转，ＡｎｇⅡ与ａ－／β－ＭＨＣ呈正相关（ｒ＝０．７９３４：Ｐ＜０．０５）。以上结果提示心肌局部ＡｎｇⅡ在运动性心肌肥大中可能具有对ａ－ＭＨＣ表达上调作用?     

运动逆转自发性高血压大鼠左心室肌球蛋白a和β重链变化的作用

本实验观察到自发性高血压大鼠（ＳＨＲ）经过１０周游泳运动，收缩压和舒张压分别比安静ＳＨＲ降低２０％和１７％，左心室肌球蛋白α－重链（ａ－ＭＨＣ）增加了２０％，β－重链（β－ＭＨＣ）降低２０％，肌原纤维ＡＴＰａｓｅ活性提高了６６％（Ｐ＜０．０５）。但两组大鼠心重／体重比值差异无统计学意义（Ｐ＞０．０５），比ＷＫＹ对照组分别高２１％和１５．３８％（Ｐ＜０．０５）。结果说明运动对ＳＨＲ大鼠左心室ＭＨＣ变化有逆转作用，而对心肌肥大程度无明显改变。提示运动训练可使病理性重塑的心脏发生生理性重塑过程，对其功能和结构的提高与改善具有积极意义。     

TASKS AND ORGANIZATION OF THE BUNDESWEHR MEDICAL SERVICE

ＴＡＳＫＳＡＮＤＯＲＧＡＮＩＺＡＴＩＯＮＯＦＴＨＥＢＵＮＤＥＳＷＥＨＲＭＥＤＩＣＡＬＳＥＲＶＩＣＥＯｂｅｒｆｅｌｄａｒｚｔＤｒ．ＳｔｅｐｈａｎＳｃｈｏｅｐｓ１．ＭｉｓｉｏｎｏｆｔｈｅＭｅｄｉｃａｌＳｅｒｖｉｃｅ，ＣｏｍｍａｎｄａｎｄＣｏｎｔｒｏｌＴｈ...     

苯那普利、芦沙坦治疗自发性高血压大鼠对肾功能及对碱性成纤维细胞生长因子、内皮素的影响

为与血管紧张素转换酶抑制剂（ＡＣＥＩ）苯那普利比较,研究新一代降压药血管紧张素Ⅱ受体拮抗剂芦沙坦对自发性高血压大鼠（ＳＨＲ）肾功能的影响,以及两药减轻 ＳＨＲ肾损害可能的机制,设立苯那普利治疗组、芦沙坦治疗组、未治疗组及正常血压对照组,治疗３个月后,检测肾功能、肾组织病理改变,血浆及肾组织内皮素（ＥＴ）水平和肾组织中碱性成纤维细胞生长因子（ｂＦＧＦ）的表达。结果显示,芦沙坦降压、延缓ＳＨＲ尿白蛋白排泄率与苯那普利比较差异无显著性意义,两治疗组肾组织病理损害轻,芦沙坦组血浆、肾组织中ＥＴ及苯那普利组肾组织中ＥＴ均明显降低,两组肾组织中ｂＦＧＦ的表达均减弱。结果表明,芦沙坦能延缓ＳＨＲ肾损害,苯那普利和芦沙坦减轻ＳＨＲ肾损害与其降低ＥＴ、抑制ｂＦＧＦ表达可能有关。     

运动性肥大心脏心肌和血浆降钙素基因相关肽含量变化

我们的前期研究发现心血管系统自身产生和分泌的调节肽参与运动性心肌肥大形成机制,但对心血管系统肽能神经纤维分泌的神经递质是否参与其机制尚不清楚。本实验采用放射免疫方法对运动性肥大心脏心肌局部降钙素基因相关肽（ｃａｌｃｉｔｏｎｉｎｇｅｎｅｒｅｌａｔｅｄｐｅｐｔｉｄｅ,ＣＧＲＰ）含量变化进行研究。结果表明,大鼠游泳运动１０周后,心系数比对照组增加３５％,心肌ＣＧＲＰ含量明显提高７０％,血浆ＣＧＲＰ含量提高４７％。这一结果提示,ＣＧＲＰ这一心血管神经调节肽在运动性心肌肥大形成中具有重要的调节作用,从已知ＣＧＲＰ作用机理推断,ＣＧＲＰ可能对运动性肥大心脏心肌收缩性的提高和肌球蛋白α重链的增加具有积极意义     

碱性成纤维细胞生长因子和内皮素在自发性高血压大鼠肾损害中的作用

为了解自发性高血压大鼠（ＳＨＲ）肾损害的程度，通过检测ＳＨＲ血浆、肾组织中内皮素（ＥＴ）和水平，碱性成纤维细胞６生长因子的表达，初步探讨ＳＨＲ肾损害的机制。将１６个月龄ＳＨＲ作为实验组，同龄ＷＫＹ大鼠作为对照组；检测ＣＣｒ、ＵＡＥ；采用放免疫射分析法大鼠血浆、肾组织中ＥＴ的水平；肾组织切片采用ＨＥ染色，ＰＡＳ染色用免疫组化检测Ⅰ、Ⅳ型胶原和ｂＦＧＦ蛋白的表达用原位杂交方法检测肾组织中ｂＦＧＦｍＲＮ     

MEDICAL TRAINING IN THE BUNDESWEHR

ＭＥＤＩＣＡＬＴＲＡＩＮＩＮＧＩＮＴＨＥＢＵＮＤＥＳＷＥＨＲＦｌｏｔｅｎａｒｚｔＤｒ．ＫａｒｓｔｅｎＯｃｋｅｒＡ．ＡＬＬ┐ＡＲＭＳＭＥＤＩＣＡＬＴＲＡＩＮＩＮＧＥａｃｈｐｈａｓｅｏｆｅｄｕｃａｔｉｏｎａｎｄｔｒａｉｎｉｎｇｐｒｏｖｉｄｅｄｔｏＢｕｎ－...     

^99mTc—MIBI门控平面心肌显像评价心肌梗塞区存活心肌—与^99mTc…

为评价＾９９ｍＴｃ－甲氧基异丁基异腈（ＭＩＢＩ）平面门控心肌显像（ＥＧＰ）在心肌梗塞患者存活心肌判断中的生，对２１例心肌梗塞患者进行了静息ＥＧＰ、静息帮动物＾９９ｍＴｃ－ＭＩＢＩ心肌单光子发现计算机断层（ＳＰＥＣＴ）显像及饥饿时静息＾１８Ｆ－脱氧葡萄糖（ＦＤＧ）正电子发射计算机断层（ＰＥＴ）正像。在２１例患者共１０５个心肌节段中，有１５个节段运动ＳＰＥＣＴ半定量分析局部＾９９ｍＴｃ－ＭＩＢＩ放射性     

人血管内皮生长因子B的重组腺病毒制备与鉴定

血管内皮生长因子Ｂ(ＶＥＧＦ Ｂ)是一种近年来发现的血管内皮生长因子家族的新成员 ,结构与ＶＥＧＦ较为相似 ,能竞争性地与ＶＥＧＦ的受体之一ＶＥＧＦＲ 1结合〔1〕。研究表明 ,尽管ＶＥＧＦ Ｂ广泛存在于多种组织 ,但以心肌和骨骼肌为主。在胎儿发育期及缺血缺氧条件下 ,ＶＥＧＦ Ｂ在心肌中的表达量显著升高〔2〕。笔者认为 ,ＶＥＧＦ Ｂ可能对心肌缺血区的血管再生起着积极的促进作用 ,而该方面的研究国内外均未见报道。本研究在获取人ＶＥＧＦ Ｂ( 186)基因的基础上构建成ＶＥＧＦ Ｂ腺病毒重组粘粒 ,为研究其在心肌缺血区基因转染后…     

自发性高血压大鼠心肌血管内皮生长因子表达水平的检测

 目的探讨血管内皮生长因子(Vascular endothelial growth factor,VEGF)在自发性高血压大鼠(Spontaneously hyper-tensive rat,SHR)心肌细胞中的表达情况,分析其与高血压时心肌毛细血管稀少及微小动脉"重塑"(remodeling)的关系.方法应用免疫组化SP染色法及计算机图像分析技术,对幼年(6周,n=15)和成年(12个月,n=15)SHR大鼠及幼年(6周,n=10)和成年(12个月,n=10)同系正常血压对照组京都Wistar大鼠(Wistar-Kyoto,WKY)心肌VEGF蛋白的表达水平进行了定量分析.结果在4组大鼠心脏各部(心房肌、心室肌、房间隔、室间隔等)心肌细胞浆中及冠状动脉各级分支的血管平滑肌细胞中均见有阳性VEGF表达,6周龄、12个月龄WKY及6周龄SHR三组间表达水平差异无统计学意义(P＞0.05),而12个月龄SHR组表达水平较其他三组均高(P＜0.05).结论随着成年SHR大鼠血压的升高,心肌及血管平滑肌细胞中VEGF蛋白的表达水平上调,可能是对高血压所致的靶器官继发性毛细血管减少的一种代偿反应,高表达的VEGF可对抗由于缺氧诱导的内皮细胞凋亡,维持其存活,并促进微血管再生.     

维甲酸对原发性高血压大鼠心肌血管平滑肌增殖的作用及其机制

目的:探讨维甲酸对自发性高血压大鼠(SHR)心肌、血管平滑肌增殖的影响和肾素-血管紧张素-醛固酮系统(RAS)所起的作用。方法:18只SHR大鼠随机分为全反式维甲酸治疗组、对照组、卡托普利治疗组,每组6只。分别予治疗组和对照组皮下注射全反式维甲酸(ATRA)10mg/Kg体重或溶媒,高血压药物治疗组予卡托普利0.25mg/Kg体重管饲,每天一次,均疗程4周。疗程结束后观察各组SHR大鼠心肌、血管平滑肌(VSMC)增殖细胞核抗原(PCNA)的变化以及心肌ACE-mRNA、ACE2-mRNA的表达。结果:维甲酸治疗组心肌、血管平滑肌增殖细胞核抗原(PCNA)表达显著低于对照组(P<0.01),卡托普利治疗组的PCNA表达也显著低于对照组(P<0.01),但维甲酸治疗组与卡托普利组比较也有显著差异(P<0.01);维甲酸治疗组ACE-mRNA的表达低于卡托普利组及对照组(P<0.01),卡托普利组ACE-mRNA的表达也低于对照组(P<0.01);而维甲酸组ACE2-mRNA的表达则高于对照组及卡托普利组(P<0.01),后两组之间则无显著差异(P>0.05)。结论:维甲酸能抑制SHR模型心肌、血管平滑肌PCNA的表达,并在增加ACE2-mRNA表达的同时减少ACE-mRNA的表达,从而有可能干预增殖性血管疾病的病程。     

Ultrasound-mediated microbubble destruction enhances VEGF gene delivery to the infarcted myocardium in rats

OBJECTIVE: To investigate the possibility of improving the delivery of vascular endothelial growth factor (VEGF) gene to the myocardium in rats by using ultrasound-mediated microbubble destruction (UMMD). METHODS: Fifteen male Wistar rats underwent left anterior descending coronary artery ligation in this study. The rats were divided into three groups 3 days after ligation. Ultrasound microbubble vectors (UMVs) attaching to pcD2VEGF121 gene were injected into the tail vein of rats with or without simultaneous echocardiographic microbubble destruction in two groups. The third group was used as control group. VEGF protein expression and formation of new blood vessels were evaluated by immunohistochemical technique during autopsy on 15 rats at 2 weeks after gene transformation. Microvascular density (MVD) in the area with myocardial infarction was counted under a microscope. RESULTS: VEGF protein expression and MVD in the ischemic myocardium were higher in the rats receiving UMMD than in the group that did not receive UMMD. CONCLUSION: UMMD is a noninvasive method to effectively improve the delivery of targeted genes to the heart.     

不同负荷运动对大鼠心肌促血管内皮生长因子表达的影响

目的 :观察并探讨不同运动负荷对大鼠心肌VEGF表达及组织学的影响。方法 :5 4雄性SD大鼠 ,随机分为对照组、中等负荷运动组和大负荷运动组 ,进行游泳训练 ,各运动组又分为训练1周 ,训练 3周和训练 5周 3个亚组 ,每组 6只。训练过程中对各组一般情况进行观察和统计。实验组和对照组同期处死 ,取左心室室前壁心肌组织块切片进行HE染色 ,VEGF表达染色 ,组织化学SDH、LDH和AKP ,5’ -N染色 ,并进行电镜观察和图像分析。结果 :对照组中 3周组和 5周组体重增长明显 (P <0 . 0 1 ) ;中等负荷运动组一般情况基本正常 ,3周组和 5周组体重出现下降 (P <0 . 0 5 ) ;大负荷运动组一般情况较差 ,3周组和 5周组体重较 1周组显著下降 (P <0 . 0 5 )。HE染色可见 ,中等负荷训练 3周组和 5周组心肌毛细血管有增多、增粗的趋势 ,大负荷运动 3周组和 5周组心肌细胞核周隙增宽、组织水肿、心肌细胞浊肿。图像分析结果显示 ,与同期对照组比较 ,中等负荷训练 1周组、3周组和 5周组VEGF着色深度 (平均灰度差 )、面积比均有不同程度增加 (P <0 . 0 1 ,P<0 . 0 5 ) ;而大负荷训练组 3周组和 5周组明显降低 (P <0 . 0 5 ,P <0 . 0 1 ) ,且染色分布不均 ,部分区域不着色。酶组织化学和电镜结果显示 ,持续大负荷训练对心肌线粒     

Sequential change of BMIPP uptake with age in spontaneously hypertensive rat model

Changes in myocardial perfusion and metabolism are often associated with myocardial hypertrophy, but there are few reports describing the serial assessment of fatty acid metabolism in hypertrophic myocardium. The aim of this study is to assess fatty acid metabolism serially in hypertrophic myocardium in spontaneously hypertensive rats (SHR) with¹²⁵I-BMIPP, a branched fatty acid analog.Methods: SHR and Wistar-Kyoto rats (WKY) as the control were divided into 4 groups (12, 15, 18 and 51 weeks after birth). The heart was extracted 10 minutes after intravenous injection of¹²⁵I-BMIPP and²⁰¹Tl at the same time. The accumulation of each radiotracer in the myocardium was counted with a well gamma counter. In addition,¹²⁵I-BMIPP uptake was corrected by²⁰¹Tl uptake (B/T).Results: The heart weight/body weight ratio was significantly higher in SHR than that in WKY (p < 0.001). In SHR, this ratio increased up to 18 weeks (12 weeks; 0.266 ± 0.005, 18 weeks; 0.281 ± 0.006: mean ± SE, p < 0.05). The¹²⁵I-BMIPP uptake tended to be significantly reduced in SHR (12 weeks; 2.373 ± 0.212, 18 weeks; 1.380 ± 0.047: mean ± SE, p < 0.05). Such a difference in BMIPP uptake was more evident when BMIPP uptake was corrected by Tl uptake (B/T), but no regional difference or heterogeneity of BMIPP distribution was observed in the hypertrophie myocardium in SHR.Conclusion: A change in fatty acid metabolism with age was observed in association with myocardial hypertrophy in this hypertensive rat model, which was well demonstrated with¹²⁵I-BMIPP and²⁰¹Tl.     

Effect of exercise training on metallothionein levels of hypertensive rats

PURPOSE: Because oxidative stress may be involved in arterial hypertension by affecting the balance between relaxing and contracting factors of vascular smooth muscle, the training-induced adaptation of antioxidant defenses could be implicated in the antihypertensive effect of chronic exercise. It has been suggested that metallothionein (MT), a metal-binding protein, plays an antioxidant role in mammals. The aim of this experiment was to study whether chronic exercise (swimming) influences both the development of arterial hypertension in spontaneously hypertensive rats (SHR) and the modification of MT levels. METHOD: Male SHR and Wistar Kyoto (WKY) rats as control were trained to swim 1 h.d-1 5 d.wk-1 for 8 wk and sacrificed 72 h after the last exercise period. MT and total thiol levels were then measured. RESULTS: Exercise training 1) reduced systolic blood pressure and heart rate in both SHR WKY rats, and 2) was associated with a decrease in hepatic and cardiac MT levels; there was an increase in the aortic MT amounts in exercised SHR only. No modifications were noted in the gastrocnemius muscle or kidneys. In exercised animals, total thiols were lower in the liver but not in kidneys. CONCLUSION: Chronic exercise induced a reduction in arterial hypertension development in SHR rats and an adaptation of the MT levels in cardiac, hepatic, and aortic tissues. Further experiments are needed to pinpoint the role of the MT in these two cases in which oxidative stress occurs.     

Serial assessment of myocardial thallium perfusion and fatty acid utilization in spontaneously hypertensive rats: assessment by autoradiography and pin-hole imaging

To evaluate the advantage of free fatty acid imaging on the detection of hypertrophied myocardium, we compared sequentially myocardial thallium and BMIPP (15-(p-iodophenyl)-3-(R,S)-methyl pentadecanoic acid) distribution in spontaneously hypertensive rat (SHR) using dual tracer autoradiography and in vivo pin-hole imaging. Autoradiography and pin-hole imaging showed uniform myocardial distribution of BMIPP and thallium within less than 27 weeks age SHR. In 40 weeks age SHR, thallium myocardial distribution showed uniform, however, BMIPP had focal decreases. Quantitative analysis of pin-hole images showed that myocardial BMIPP and thallium uptake ratio decreased according to the ages of SHR. Our data suggest that hypertension is associated with uniform myocardial perfusion and focal alternation in the substrate used for the performance of myocardial work. Based on the above autoradiographic and in vivo pin-hole imagings, I-123 BMIPP imaging may have a potential for early detection on hypertrophic myocardium compared to thallium perfusion in clinically hypertensive patients.     

腺病毒介导的VEGF-B基因促血管内皮细胞增殖作用的研究

为观察腺癌毒素介导的血管内皮细胞生长因子B（VEGF－B）基因体外转染对血管内皮细胞的促增殖作用，构建编码人VEGF－B基因的复制缺陷的重组腺病毒载体，体外转染鼠主动脉血管内皮细胞（RAECs），应用RT－PCR和Western blot检测外源VEGF－B的表达，应用四唑盐（MTT）观察转染后RAECs的增殖。结果发现，RAECs可有效地被重组腺病毒载体感染，并能成功转录和表达VEGF－B基因和蛋白，在转染后细胞培养上清中检测到VEGF－B蛋白的表达，对RAECs有显著促增殖作用。提示重组腺病毒载体介导的人VEGF－B基因有血管新生作用，可用于缺血性心脏病的治疗。