家兔实验压力性左心室肥厚心肌的超微结构变化

用光镜和电镜技术,动态地观察了家兔实验性压力性左心室肥厚心肌细胞形态结构的定性变化,着重于超微结构方面,试图从形态学角度探讨心肌肥厚发生、发展的某些规律。     

西拉普利对自发性高血压大鼠心肌超微结构损害的逆转作用

对自发性高血压大鼠及正常对照鼠进行研究。分为ＳＨＲ治疗前、后以及不作治疗组和相应月龄ＷＫＹ５组。其中治疗组给予口服西拉普利３个月。用细胞立体计量法测定各组大鼠左心室心肌超微结构的改变。发现（１）ＳＨＲ组降血压高于同龄ＷＫＹ外，存在心肌细胞线粒体密度增高，比表面降低及肌节宽度延长，肌束及核周水肿，胶原区扩大等。（２）西拉普利在有效地控制ＳＨＲ的血压的同时能减轻ＳＨＲ的上述心肌超微结构损害。     

西拉普利对自发性高血压大鼠心肌超微结构损害的逆转作用

对自发性高血压大鼠（ＳＨＲ）及正常对照鼠（ＷＫＹ）进行研究。分为ＳＨＲ治疗前、后以及不作治疗组和相应月龄ＷＫＹ５组，其中治疗组给予口服西拉普利３个月。用细胞立体计量检测法测定各组大鼠左心室心肌超微结构的改变，发现（１）ＳＨＲ组除血压高于同龄ＷＫＹ外，存在心肌细胞线粒体密度增高，比表面降低及肌节宽度（Ｚ线长度）延长，肌束及核周水肿，胶原区扩大锌。（２）西拉普利在有效地控制ＳＨＲ的血压的同时能减轻ＳＨＲ的上述心肌超微结构损害。揭示西拉普利能逆转ＳＨＲ心肌超微结构损害，进而逆转左室肥厚及使并发症减少。     

运动性心脏肥大心肌细胞超微结构改变及意义

目的研究运动性心脏肥大时心肌细胞超微结构的变化规律及运动对心肌细胞的影响,为防治运动性心脏猝死提供科学依据。方法雄性SD大鼠31只。对照组不训练;有氧训练组（Ae组）每天训练75min;过度训练组（0e组）大鼠尾部负重（体重的5％）,每天训练180min。每周5天,共12周。取材后电镜观察。结果Ae组：心肌细胞线粒体数目增多且轻度肿胀,基质尚均匀,线粒体膜完整。偶见少量电子密度高的致密体。细胞核增大,核周隙略增宽,偶见核膜皱缩呈齿状。0e组：线粒体数目比Ae组明显增多,肿胀更明显;有些线粒体中嵴紊乱,融合,甚至消失,基质颗粒消失;有的线粒体腔内出现大而不规则的絮状致密物,膜结构不清。细胞质内可见多个电子密度高的致密体。细胞核明显内陷,核周隙增宽。核浆不均匀,异染色质在核边缘部聚集,并有染色质明显凝聚,呈粗块状。结论运动使心脏发生适应性改变,同时也导致心肌细胞发生与衰老细胞相似的病理性改变。随着运动强度的增大,这些病理性变化越严重,甚至导致心肌细胞死亡。因此,过度运动对心肌细胞产生不利影响。     

开搏通加复方丹参滴丸治疗高血压心肌重构的观察

目的:观察开搏通加复方丹参滴丸对高血压心肌重构的影响。方法:高血压合并左室壁及室间隔肥厚70例患者被分为治疗组(45例)和对照组(25例),用药前及用药后3、9个月各查二维超声心动图1次,测量用药前、后的左室壁、室间隔厚度,左室内径,射血分数,E/A值等数据。结果;治疗组左室壁、室间隔厚度,左室内径均小于对照组,E/A值高于对照组(P<0.005),射血分数两组无差异。结论:开搏通加复方丹参滴丸合用能有效地逆转高血压心肌重构。     

高血压诱导大鼠心肌肥大过程中Caspase募集域的凋亡抑制蛋白表达水平的变化

目的探讨高血压致心肌肥大发生发展过程中Caspase募集域的凋亡抑制蛋白(ARC)表达的变化规律。方法选取Wistar大鼠45只,按随机数字表法分为腹主动脉缩窄组、假手术组、对照组(每组15只),腹主动脉缩窄组用腹主动脉缩窄的方法建立高血压心肌肥大模型,每组又按术后1、2、3、4、6周时段平均分为5个亚组。并在心肌肥大形成的不同阶段提取组织蛋白,采用免疫沉淀法检测心肌中ARC的表达水平及其磷酸化状态。结果与假手术组相比,腹主动脉缩窄组血压、左心系数在术后第4周明显升高,病理学结果显示在术后第4周肌纤维增粗,心肌细胞肥大。由Western blot和灰度值分析结果可以看出,在心肌肥大过程中未见ARC表达水平有明显变化,而ARC磷酸化水平在术后第4周明显降低,与假手术组和对照组相比,ARC表达水平差异无统计学意义(P>0.05),第4周和第6周ARC的磷酸化水平差异有统计学意义(P<0.05),对照组与假手术组之间ARC磷酸化水平差异无统计学意义(P>0.05)。结论 ARC磷酸化水平的明显降低可能是导致高血压致心肌细胞肥大的重要分子基础之一。     

螺内酯抗CaN依赖的肾性高血压大鼠心肌肥大的研究

目的观察螺内酯(Spironolactone,Spiro)抗钙调神经磷酸酶(calcineurin,CaN)依赖的肾性高血压大鼠心肌肥大的作用.方法20只Wistar大鼠随机分为3组两组采用一肾一夹模型制造肾性高血压,其中spiro组(n=7)给予螺内酯灌胃,op组(n=7)予水灌胃;假手术组(sham op n=6)只给予水灌胃.称重法测定心重比,发色底物法测CaN活性;同时用免疫组织化学染色方法,观察心肌中CaN及活化T细胞核因子(nuclear factor of activatedT cell,NFAT)的表达.结果肾性高血压大鼠经螺内酯灌胃4周,其心重比较未干预组明显降低(P＜0.05),心肌肥大受到抑制,同时发现心肌中CaN活性较未干预组显著下降,免疫组化显示螺内酯干预组心肌中CaN及NFAT表达降低.结论螺内酯抑制肾性高血压心肌肥大的机制与其下调心肌胞浆中CaN表达及其活性有关.     

L—精氨酸对肾性高血压心肌肥厚大鼠左室超微结构的影响

目的 观察L－精氨酸（L－Arg)对血管性高血压心肌肥厚大鼠左室肌超微结构的影响。方法 L－Arg治疗高血压心肌肥厚大鼠8周后处死,镜检左室心肌亚细胞结构改变。结果 经8周治疗后可见L－Arg治疗组心肌细胞肌丝排列整齐、核规则、核仁清晰、线粒体形态结构正常。结论 L－Arg能有效保护心肌亚细胞结构。     

心肌肥大过程中的信号转导

心肌肥大是一常见而重要的临床的现象,它的发生发展涉及到诸多因素,机制尚未完全阐明.本文从酪氨酸激酶受体gp130、小G蛋白家族、蛋白激酶C、丝裂素活化蛋白激酶和钙信号等方面介绍心肌肥大相关信号转导途径的研究近况,并对今后的研究方向作一探讨.     

Ultrastructural changes during myocardial hypertrophy and its regression: Long-term effects of nifedipine in adult spontaneously hypertensive rats

Summary Nifedipine (20mg/kg/day) was given to 15-week-old spontaneously hypertensive rats for 20 weeks (SHR-N,n=8). Comparison was done with sex-matched 15-week-old SHR (SHR-15,n=7), untreated 35-week-old SHR (SHR-C,n=10), 15-week-old normotensive Wistar-Kyoto rats (WKY-15,n=15), and 35-week-old WKY (WKY-15,n=5). Light and electron microscopic data on the subepicardial, middle, and subendocardial layers and papillary muscles of the left ventricle were compared among the five rat groups. In SHR-N, blood pressure was significantly reduced by nifedipine, but was higher than in WKY-35 (199±11 mmHg vs 121±13mmHg). The left ventricular weight/body weight ratio was much lower in SHR-N than in SHR-C, and was even below the baseline value in SHR-15. In addition, cardiac myocyte diameter was much smaller in each myocardial layer of SHR-N than in SHR-C, and was similar to the findings in SHR-15, but still larger than in WKY-35. The interstitial area ratio was markedly reduced in SHR-N and did not differ from that in SHR-15 or even WKY-15, while capillary density was significantly greater than in SHR-C and comparable to that in WKY-35. In SHR-C, large fibrotic foci were common, and many hypertrophic cardiac myocytes showed various degenerative changes including those of mitochondria and widening of the intermyofibrillar spaces. These changes were rarely seen in SHR-N. The intracellular volume ratio of myofibrils did not differ between SHR-N and WKY-35, but was significantly decreased in SHR-C, whereas that of mitochondria did not differ between SHR-N and SHR-C or WKY-35. These findings indicate that despite only a moderate suppression of hypertension, long-term nifedipine treatment caused regression of left ventricular hypertrophy, with cardiocyte hypertrophy, interstitial fibrosis, degenerative changes, and subcellular remodeling being reversed to the baseline levels in SHR-15. In addition, the capillary density was increased to that seen in WKY-35.     

Myocardial contractility and ventricular myosin isoenzymes as influenced by cardiac hypertrophy and its regression

Summary Changes in myocardial contractility and ventricular myosin isoenzymes were examined during pressure-overloaded cardiac hypertrophy in rats. Effects of regression of cardiac hypertrophy were also examined. Cardiac hypertrophy was induced by abdominal aortic constriction in 7-week-old male Wistar rats. Regression of cardiac hypertrophy was obtained by opening the aortic band. Myocardial contractility was estimated by measuring isometrically developed tension and maximum rate of tension rise (+dT/dtmax) in isolated left-ventricular papillary muscles perfused with Tyrode solution (32°C, pH 7.4, bubbled with 95% O₂·5% CO₂, stimulation frequency: 0.2 Hz). Left-ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis and the isoenzyme pattern was determined by densitometry. Isometrically developed tension (T) in hypertrophic myocardium remained unchanged, but ±dT/dtmax decreased as compared with hearts of normal rats. Decreased ±dT/dtmax recovered near to the level in normal rats by regression of cardiac hypertrophy. Leftventricular myosin isoenzyme pattern shifted towards VM-3 in hypertrophied myocardium and shifted again toward VM-1 by regression of cardiac hypertrophy. In conclusion, myocardial contractility and ventricular myosin isoenzymes were changed in pressure-overloaded hypertrophy in rats and these changes were reversible to a normal level by regression of cardiac hypertrophy.     

曲美他嗪对异丙肾上腺素所致大鼠心肌肥厚的影响

目的探讨曲美他嗪（TMZ）对异丙肾上腺素（ISO）致大鼠心肌肥厚的影响及可能的作用机制。方法30只Sprague-Ddwley（SD）大鼠,随机分为3组。正常对照组、ISO组、TMZ组,每组10只。通过大剂量注射ISO制成心肌肥厚模型,以TMZ干预,观察心肌组织病理学变化和心肌细胞超微结构改变,计算心脏质量/体质量（HW/BW）,测定心肌三磷酸腺苷（ATP）、丙二醛（MDA）、超氧化物歧化酶（SOD）和血清乳酸脱氢酶（LDH）、肌酸激酶（CK）含量。结果TMZ组与ISO组比较,HW/BW、LDH、CK、SOD和ATP有显著差异（P<0.05）,而与正常对照组比较无显著差异。TMZ组心肌组织病理损伤程度及细胞超微结构改变程度,较ISO组明显减轻,而接近正常对照组。结论TMZ可拮抗ISO所致的大鼠心肌肥厚,其机制可能与改善心肌能量代谢、提高组织对缺氧的耐受力、消除氧自由基等有关。     

一氧化氮合酶mRNA在压力超负荷心肌肥厚中的作用

目的:研究一氧化氮合酶(NOS)mRNA在心肌肥厚发生发展中的作用以及卡托普利防治心肌肥厚的机制。方法:采用腹主动脉狭窄术建立压力超负荷心肌肥厚动物模型,应用RT-PCR方法于术后1、2、4周,分别检测对照组、心肌肥厚组和卡托普利组大鼠左心室心肌组织NOS mRNA表达的变化。结果:①与对照组相比,术后1、2、4周心肌肥厚组大鼠左室重/体重(LVW/BW)指标及SBP均显著升高;左心室eNOS mRNA表达降低,iNOS mRNA表达升高,nNOS mRNA表达无明显变化。②与心肌肥厚组相比,术后1、2、4周卡托普利组大鼠LVW/BW及SBP均显著降低;左心室eNOS mRNA表达升高,iNOS mRNA表达降低,接近对照组。结论: eNOS和iNOS参与心肌肥厚的发生发展过程,但二者起不同作用。卡托普利防治心肌肥厚的作用可能与其调节NOS mRNA表达密切相关。     

冠脉循环微血管病变与老年高血压左室肥厚患者的心脏事件

目的　探讨老年高血压左室肥厚患者冠脉循环微血管病理改变与心脏事件的关系。方法　从我院 195 4～1996年间连续尸检 3195例的心脏标本中选取≥ 6 0岁 ,经临床和病理证实的高血压患者共 15 8例 (高血压 71例 ,高血压合并冠心病 6 2例 ,高血压合并冠心病和糖尿病 2 5例 )进行下列测定 :(1)左室肥厚 (LVH)分级 ;(2 )冠状动脉粥样硬化 (CAS)狭窄分级 ;(3)主动脉粥样硬化 (AAS)分级 ;(4)心肌微动脉密度 :直径 10～ 6 0 μm有内弹力板的心肌微动脉数 ;(5 )心肌微动脉壁腔比值 ;(6 )心肌毛细血管密度及其内皮细胞面积。结果　本组病理资料Logistic分析证实 ,老年高血压左室肥厚患者心脏事件的影响因素 ,按相关程度高低依次为心肌微动脉壁腔比值 (r =0 .1783,P=0 .0 0 5 5 ,OR=12 .72 0 4) ,CAS (r=0 .1738,P =0 .0 0 6 4,OR=2 .340 9) 及心肌微动脉密度 (r=- 0 .12 2 3,P=0 .0 30 4,OR =0 .6 10 1)。结论　冠脉循环微动脉病变程度及CAS程度是影响老年高血压左室肥厚患者心脏事件发生率的主要因素 ,应引起进一步重视     

Administration time–dependent effect of nitrendipine on the reduction of cardiac hypertrophy in spontaneously hypertensive rats

The influence of administration time of nitrendipine on the regression of cardiac mass was studied in spontaneously hypertensive rats (SHR). Nitrendipine (100 mg/kg) was given once daily at 10 or 10 for 16 weeks. Similar reductions of the trough blood pressure were observed in both groups. Cardiac biventricular mass in the animals dosed at 10 was significantly less than that in the vehicle-treated rats, whereas in the rats dosed at 10 no significant reduction was noted in the cardiac mass. These data suggest that the administration time of nitrendipine has a different effect on the regression of cardiac hypertrophy in SHR.     

卡托普利长程干预对自发性高血压大鼠左室肥厚及c-myc基因表达的影响

目的:以自发性高血压大鼠（SHR）为研究对象,探讨血管紧张素转换酶抑制剂（ACEI）卡托普利长程治疗,对SHR左室肥厚（LVH）的改善及其可能机制。方法:20周龄雄性SHR20只,随机分为卡托普利干预组（Cap组）和对照组（Con组）,每组10只,观察卡托普利干预后13周内血压变化,并于观察期末测左心室质量/体质量（LVW/BW）及左心室组织c myc基因的表达。结果:卡托普利（100mg·kg-1·d-1）可使SHR的SBP显著降低,治疗4周后达最大降压效应,且该效应于第13周末仍可维持（P<0.01）;Cap组LVW/BW显著低于Con组（3.42±0.21mg/gvs3.96±0.18mg/g,P<0.01）,c myc表达亦显著低于Con组（0.74±0.16Avs1.24±0.21A,P<0.01）。结论:卡托普利长程治疗降压效应确切,并能显著改善SHR左心室肥厚,抑制原癌基因c myc表达可能是其作用机制之一。     

解耦联蛋白-2与压力超负荷大鼠心肌肥厚中的细胞凋亡

目的探讨心肌解耦联蛋白-2（ucP2）与压力超负荷心肌肥厚中心肌细胞凋亡的关系。方法采用腹主动脉缩窄法建立大鼠压力超负荷模型,假手术大鼠作为对照组。术后1,2,4,7,14,21,30d,RT-PCR法测定UCP2mRNA含量,TUNEL法检测心肌细胞凋亡水平。结果（1）与对照组比较,压力超负荷组在术后4d UCP2 mRNA含量上调,并持续增高至30d。（2）压力超负荷组心肌细胞凋亡在术后1d即升高,在4d时进入高峰期并持续至7d,其后低水平持续存在,直至实验结束。而对照组未发现凋亡细胞。结论UCP2可能参与了压力超负荷心肌肥厚中细胞凋亡的调控,但其确切机制有待进一步研究。     

Role of angiotensin II type 2 receptor during regression of cardiac hypertrophy in spontaneously hypertensive rats

We previously reported that the AT₁ receptor antagonist valsartan and the angiotensin converting enzyme (ACE) inhibitor enalapril decrease DNA synthesis and stimulate apoptosis in interstitial fibroblasts and epicardial mesothelial cells during regression of ventricular hypertrophy in spontaneously hypertensive rats (SHR). To examine the role of the AT₂ receptor in this model, we studied hearts from SHR treated with valsartan or enalapril either alone or combined with the AT₂ antagonist PD123319 for 1 or 2 weeks. Apoptosis was evaluated by quantification of DNA fragmentation or by TUNEL labeling. At 1 week, valsartan significantly increased ventricular DNA fragmentation, increased apoptosis in epicardial mesothelial cells, and decreased DNA synthesis. At 2 weeks, ventricular DNA content and cardiomyocyte cross-sectional area were significantly reduced. These valsartan-induced changes were attenuated by PD123319 co-administration. However, valsartan-induced increases in apoptosis of left ventricular interstitial non-cardiomyocytes was unaffected by the AT₂ blocker. Enalapril-induced changes were similar to those observed with valsartan but were not affected by co-treatment with PD123319. These results demonstrate that AT₁ and AT₂ receptors act in a coordinated yet cell-specific manner to regulate cell growth and apoptosis in the left ventricle of SHR during AT₁ receptor blockade but not ACE inhibition.     

高血压患者脉压与左心室肥厚构型及心功能的关系

目的　探讨药物规则治疗下高血压病 (EH)患者的脉压 (PP)与左心室肥厚 (L VH)构型及心功能的关系。方法　本研究回顾性分析 176例有或无 L VH的 EH患者的 PP与 L VH构型及心功能的相关性。结果　 1不对称性室间隔肥厚 (ASH)、对称性室间隔肥厚 (CH)及扩张性肥厚 (DH)三型肥厚组的 PP与无 L VH组相比 ,有明显的差别 ,CH和 DH组较大 (P均 <0 .0 1) ,尤以 DH组较甚。2随着 PP增大 ,左心室收缩及舒张功能均明显的降低。3L ogistic回归分析显示 ,PP与 EH患者左心功能不全发生存在明显的相关性 ,PP每增加 10 m m Hg,左心功能不全增加 30 % (95 % CI:1.2 3～ 1.37,P<0 .0 0 0 1) ;在对年龄和 EH病程进行校正后 ,PP每增加 10 m m Hg显示增加左心功能不全发生率 19% (95 % CI:1.13～ 1.2 5 ,P<0 .0 0 0 1)。结论　在药物规则治疗的 EH患者中 ,PP与 L VH构型具有一定的联系 ,PP是左心功能不全发生的一个重要和独立的相关因素 ;且随着 PP增大 ,左心室收缩及舒张功能均明显的降低。