长期糖尿病大鼠心脏肾上腺素受体的改变

本文观察了长期糖尿病大鼠心脏β肾上腺素受体，α１肾上腺素受体及其亚型的改变。在功能实验中，糖尿病大鼠左心耳对异丙肾上腺素与苯肾上腺素所介导的正性肌力作用无显著改变，而放射配体结合实验结果表明，糖尿病大鼠心肌β受体与α１受体数目均显著下降（Ｐ＜０．０５）；在α１受体中，α１Ｂ受体亚型所占的比例显著增高，由于在大鼠心脏主要由α１Ｂ亚型受体介导正性肌力作用，上述亚型的改变可部分解释糖尿病大鼠心肌α１受体     

缺氧复合运动大鼠心脏的适应性改变

目的 :观察在缺氧条件下运动对大鼠心脏功能、毛细血管密度、静息血流量的影响 ,探讨在缺氧条件下 ,适当运动有无促进缺氧习服的可能性。方法 :48只Ｗｉｓｔａｒ大鼠分为 3组 :Ⅰ组 ,常压对照组 ;Ⅱ组 ,单纯缺氧组 ;Ⅲ组 ,缺氧复合运动组。Ⅱ、Ⅲ两组大鼠每天置低压舱内持续减压 2 3ｈ/ｄ ,共 5周。第Ⅲ组大鼠先升至模拟 40 0 0ｍ ,停留 30ｍｉｎ后进行游泳运动 (游泳 1ｈ/ｄ ,6ｄ/周 ) ,1ｈ后升至 50 0 0ｍ。Ⅱ、Ⅲ两组缺氧条件相同。 5周后在模拟 40 0 0ｍ高原用心导管技术测定心功能、放射性微球法测定心肌血流量、酶组化法显示大鼠心肌…     

大鼠胚胎心脏发育过程中凋亡及凋亡基因表达的检测

目的:检测大鼠胚胎心脏发育过程中凋亡及凋亡基因表达,进一步明确心脏发育的调控机制.方法:采用半定量RT-PCR、免疫组织化染色SABC法和TUNEL法对E11～E19 SD大鼠心脏凋亡细胞和p53mRNA、Bax蛋白表达进行测定.结果:p53和BAX在E11～E19表达均呈逐渐增强再减弱的趋势,表达的高峰位于E14.TUNEL染色结果显示,E11～E19均可见凋亡小体.E11时散在分布于心内外膜;E13主要分布于心尖;E14时表达最强,主要分布于心房和心腔分隔处;E16后表达减弱,分布主要集中于心腔内壁.结论:大鼠心脏发育中后期均有凋亡存在;E14为凋亡表达高峰时期;p53和Bax在促进心肌细胞凋亡、心脏外形和心腔形成方面起到重要的作用.     

心肌梗死大鼠缺血心肌中内皮抑素的表达

目的： 观察心肌梗死后大鼠不同时间缺血心肌中内皮抑素的表达及其与新生血管密度和血管内皮生长因子（VEGF）的关系。 方法： 32只心肌梗死SD大鼠随机分为心肌梗死后7、14、21、28 d 4个组，以假手术组作为正常对照组，每组8只。应用免疫组织化学染色方法，观察各组心肌梗死大鼠缺血心肌中内皮抑素、VEGF 的表达和新生血管密度。 结果： 心肌梗死大鼠缺血心肌中内皮抑素的表达明显增加，弥散分部于心肌细胞和组织间隙，第7 d表达量最高，至14、21、28 d表达量逐渐降低，28 d基本降至基础水平，与VEGF表达的变化趋势一致，并与新生血管密度相关。 结论： 内皮抑素在心肌梗死大鼠的缺血心肌中表达增加，与VEGF的动态变化一致，并与新生血管密度呈正相关，提示内皮抑素可能参与缺血心肌血管新生的调节。     

低氧诱导因子-1α参与低氧预处理诱导的心肌血管生成

目的：研究低氧诱导因子-1α（HIF-1α）在低氧预处理（HPC）诱导心肌血管生成中的作用,并探讨其细胞信号转导的机制。方法：雄性SD大鼠随机分为对照组和HPC组。动物置于低氧仓内，持续通入10% O2和90% N2 4 h复制低氧预处理模型。用Ⅷ因子免疫组化染色检测HPC后7 d和21 d心肌组织微血管密度。制备心肌组织蛋白提取物，分别以磷酸化的细胞外信号调节激酶（ERK1/2）抗体和HIF-1α抗体检测HPC后1 d、7 d和21 d p-ERK1/2活性及HIF-1α表达。结果：HPC后7 d和21 d心肌组织微血管密度分别较对照组高36.99%和37.76%（均P<0.01）；p-ERK1/2活性在HPC后1d 较对照组高18.67%；HPC诱导HIF-1α的表达，其表达高峰出现在HPC后1 d。结论：HPC可以促进心肌微血管生成，其机制涉及ERKs活化和HIF-1α表达上调。     

间歇性低氧预处理对缺血心肌的促血管生成作用的实验研究

目的:采用冠状动脉左前降支部分结扎的方法复制慢性心肌缺血的动物模型,观察间歇性低压低氧预处理的促血管生成作用。方法: 成年雄性新西兰家兔29只,体重2.0-2.5 kg,随机分为3大组:正常组(N组,n=7),对照组(C组,n=11)和间歇性低氧预处理组(H组,n=11)。C组、H组行冠状动脉左前降支部分结扎,H组动物进行间歇性低氧预处理(5 000 m,6 h/d,连续7 d者为H1组,42 d者为H2组),按计划完成实验后测定血管内皮生长因子mRNA (VEGFmRNA)、低氧诱导因子-1 α mRNA (HIF-1 α mRNA)、内皮细胞一氧化氮合酶mRNA(eNOSmRNA)及血管内皮生长因子(VEGF)蛋白表达及毛细血管密度。结果: 间歇性低氧预处理VEGF mRNA、HIF-1 α mRNA、eNOS mRNA及VEGF蛋白持续增加,毛细血管密度增高。结论: 间歇性低氧预处理能促进慢性缺血心肌内的血管生成。     

长期糖尿病大鼠心脏β肾上腺素受体及其亚型的改变

目的：观察长期糖尿病大鼠心脏β肾上腺素受体（β－ＡＲ）及其亚型的改变。方法：链脲佐菌素（ＳＴＺ）诱导糖尿病大鼠动物模型,用放射配体结合实验和离体左心房收缩功能实验。结果：糖尿病大鼠心脏β－ＡＲ的最大结合容量下降３４％（Ｐ＜００５）,ＫＤ值不变。ＣＧＰ２０７１２Ａ竞争抑制曲线两位点分析显示β１－和β２－ＡＲ之间比例未发生改变。糖尿病组异丙肾上腺素（ｉｓｏｐｒｏｔｅｒｅｎｏｌ,ＩＳＯ）激动β－ＡＲ介导的最大收缩反应（Ｒｍａｘ）较对照组下降６４％（Ｐ＜００５）,ｐＤ２值显著增大（Ｐ＜００５）,ＣＧＰ２０７１２Ａ阻断β１－ＡＲ后,β２－ＡＲ介导心肌的Ｒｍａｘ不变,而ｐＤ２值显著高于对照组（Ｐ＜００５）;ＩＣＩ１１８５５１阻断β２－ＡＲ后,β１－ＡＲ介导心肌的Ｒｍａｘ显著低于对照组（Ｐ＜００５）,ｐＤ２值与对照组相比无显著差异。结论：长期糖尿病大鼠心脏β－ＡＲ总数明显下调,且β１－和β２－ＡＲ下调的程度相同;β－ＡＲ对ＩＳＯ敏感性的增加,主要是由β２－ＡＲ的改变引起,β－ＡＲ介导的最大收缩反应的降低,是由β１－ＡＲ的改变引起。     

HIF-1介导的自噬在心脏疾病中的研究进展

低氧诱导因子1(HIF-1)通过调控靶基因表达维持机体供氧和需氧平衡,保持细胞氧稳态,并调节缺血心肌自噬水平,其靶基因表达产物BNIP3蛋白参与此调节过程。     

自发性高血压大鼠心脏α1肾上腺素受体及其亚型的改变

目的：观察４月龄自发性高血压大鼠（ＳＨＲ）心脏α１肾上腺素受体（α１－ＡＲ）及其３种亚型分布与功能的改变。方法：采用离体左心房收缩功能实验和放射配体结合实验。结果：ＳＨＲ与Ｗｉｓｔａｒ大鼠相比，（１）心脏α１－ＡＲ总密度无显著变化，但对去甲肾上腺素（ＮＥ）的敏感性显著增加（Ｐ＜００５）；（２）心脏α１Ａ－ＡＲ数量无明显改变，而α１Ｂ－ＡＲ增加，α１Ｄ－ＡＲ减少，但３种亚型受体在介导ＮＥ所致心肌正性变力效应中均无显著改变。结论：提示ＳＨＲ心脏α１－ＡＲ对ＮＥ敏感性的增加可能与受体后信号转导和／或兴奋收缩耦联的增强有关，其中尤以α１Ｄ－ＡＲ最为明显     

急性低压低氧大鼠氧比传导特征的实验研究

单位氧耗量氧比传导，简称氧比传导（ＭＯ２－ＳＣ）是新近提出的一项综合评价机体低氧生理性适应水平高低的客观指标。本实验于低压舱内模拟高原低压性低氧条件（相当于６０００ｍ海拔高度），研究了大量气体交换系统ＭＯ２－ＳＣ的适应特征及规律。结果发现，低氧条件下，从吸入气（Ｉ）至肺泡气（Ａ）（Ｉ→Ａ）、Ａ至脉动血（ａ）（Ａ→ａ）、ａ至混合静脉血（ｖ↑－）（ａ→ｖ↑－）及Ｉ→ｖ↑－间氧分压差明显减小（Ｐ〈０．０     

Myocardial capillarity in acclimation to hypoxia

Capillarity, O₂ diffusion distances and fiber crosssectional growth were measured in the hearts of guinea pigs exposed early during growth to hypobaric hypoxia (P _B=430 torr,PO₂=90 torr). Twelve 5-week old males were maintained in a hypobaric chamber for 4–14 weeks. Their hearts were perfusion-fixed via the aorta with a 2.5% glutaraldehyde, 1% formaldehyde buffered solution; blocks were cut from left (LV) and right (RV) ventricles, post-fixed in OsO₄, dehydrated and embedded in Spurr medium. Blocks were cut transversely to fiber orientation, 0.5 m thick, stained with Toluidine Blue, and photographed at 400 x. Number and location of capillaries and fiber cross-sectional areas (FCSA) were scored from these photographs and from those of normoxic controls. Growth rates were similar for control and hypoxic guinea pigs. As animals grew, LV and RV weights increased linearly with body weight. Hypoxic guinea pigs had LV weights similar to controls but the RV showed varying degrees of hypertrophy. Control and hypoxic guinea pigs showed similar linear increases in FCSA with ventricular weight, suggesting that hypertrophy was due to increased FCSA. Capillary density (CD) decreased and capillary-to-fiber ratio (CF) increased with FCSA, and O₂ diffusion distances lengthened in LV and RV of animals in both groups. CD and CF were higher and O₂ diffusion distances were shorter in most hypoxic animals compared to controls. When RV hypertrophy was large (RV>0.7 g) and failure imminent, CD, CF and O₂ diffusion distances were similar to controls suggesting that in these hearts oxygenation was impaired.Supported by NIH grants HL-18145 and HL-28849Supported by NIH Post Doctoral Fellowship HL-06527     

Anoxidative work and metabolism of isolated perfused rat hearts as influenced by artificially increased heart rate

Summary Under anoxidative conditions the capacity of mechanical activity and the metabolism of isolated rat hearts were studied at various pacemaker-induced heart rates. Isovolumic work decreased to about one third of its initial rate within a 5 min period of anoxidative perfusion and remained almost constant during a further 10 min observation time. Increased heart rate (100, 175, and 250 b.p.m.) was associated with an increase in left ventricular diastolic pressure and with decreases in systolic pressure and maximal dp/dt. Lactate production, tissue creatine phosphate and inorganic phosphate had no consistent relationship to heart rate, whereas tissue ATP decreased with increasing heart rate. It is concluded that the rate of anoxidative isovolumic work cannot be increased by raising the heart rate since anoxidative carbohydrate breakdown cannot be more activated than at the lowest heart rate studied and cannot exceed a rate of 30 mol hexose/min·g dry weight in the perfused heart.     

线粒体渗透转换孔在肿瘤坏死因子α诱导的抗心肌缺氧/复氧损伤中的作用

目的：研究肿瘤坏死因子α（TNFα）诱导的抗心肌缺氧/复氧损伤的保护作用是否与抑制线粒体渗透转换孔的开放有关。 方法： 采用离体大鼠心脏灌流方法，结扎冠状动脉左前降支30 min和复氧120 min复制局部缺氧/复氧损伤模型，测定心肌梗死面积、冠脉流出液中乳酸脱氢酶（LDH）含量及各项心室力学指标。 结果： 与单纯缺氧/复氧组相比，1×104 U/L TNFα预处理明显降低心脏缺氧/复氧后的梗死面积和复氧期冠脉流出液中LDH含量，促进左室发展压、左室做功和左室舒张末压力的恢复。线粒体渗透转换孔开放剂atractyloside和钙激活钾通道阻断剂paxilline减弱了TNFα的作用。 结论： TNFα诱导的抗心肌缺氧/复氧损伤的保护作用可能与其抑制线粒体渗透转换孔的开放及促进钙激活钾通道的开放有关。     

Arterial pressure and heart rate changes during natural sleep in rat

Mean arterial pressure and heart rate data during quiet wakefulness and phases of sleep in conscious rat are sampled by a computer at a rate of 100/sec. Average values and variability expressed as standard deviation are computed for each recording session. Mean arterial pressure and heart rate and their variability decrease from quiet wakefulness to synchronized sleep. During desynchronized sleep, mean arterial pressure increases to the level of quiet wakefulness and is more variable than during synchronized sleep. Heart rate is lower and more uniform during sleep than during quiet wakefulness, and there is no difference between synchronized and desynchronized sleep except that a greater variability occurs during desynchronized sleep. The study shows that characteristic and specific cardiovascular changes accompany the phases of sleep and that a hierarchy of arterial pressure is present during the resting behavior in rat.     

Structural changes in the rat myocardium during adaptation to mountain hypoxia

Changes in weight indices for different parts of the heart, the area of cross sections of the myocytes, and vascularization of the myocardium during adaptation to hypoxia were studied in experiments on rats exposed to high-altitude hypoxia (3200 m above sea level). The morphological manifestation of compensatory and adaptive reactions of the rat heart to hypoxia is an increase in its weight, chiefly on account of hypertrophy of the myocardium of the right ventricle. Increasing hypertrophy of the myocardium is accompanied by the corresponding increase in its vascularization.Khirghiz Research Institute of Obstetrics and Pediatrics, Frunze. (Presented by Academician of the Academy of Medical Sciences of the USSR A. V. Smol'yannikov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 88, No. 10, pp. 498–500, October, 1979.     

缺氧对急性心肌梗死后3周大鼠心室肌细胞持续性钠电流的影响

目的：研究缺氧对急性心肌梗死（AMI）大鼠心室肌细胞持续性钠电流的影响，以期更进一步探讨急性心肌梗死后心律失常的发生机制。 方法： 采用结扎大鼠冠状动脉左前降支建立AMI动物模型,应用膜片钳全细胞记录方法,观察AMI 3周心室肌外膜梗死区细胞持续性电流（INap）的变化。 结果： 常氧条件下，假手术组（n=9）的INap电流密度为0.144±0.022（pA/pF）,心梗组（n=9）的INap电流密度为0.121±0.013（pA/pF）,明显低于假手术组(P<0.01), 以上两组的INap 均可被河豚毒素（TTX）阻断。缺氧条件下，假手术组和心梗组的INap均随着缺氧时间的延续而增大，但假手术组INap的增大明显大于心梗组，两组的INap均可被谷胱甘肽（1 mmol/L）所阻断。 结论： 急性心肌梗死后，无论是在常氧或是再次缺氧情况下，心肌梗死区与非梗死区细胞INap的大小均存在差异，造成心肌复极离散度增大，可能是导致AMI后出现折返性室性心律失常的原因之一。