脓毒症心肌线粒体改变与干预的研究进展

约50%的脓毒症患者合并心脏收缩功能降低和心输出量减少,约11.4%患者甚至出现心功能衰竭。目前认为,脓毒症时心肌线粒体形态和功能的改变是心肌收缩功能降低的重要原因。长期以来人们对脓毒症时的心肌线粒体改变与干预的基础和临床研究开展了大量的实验。本文就近年来国内外有关脓毒症时心肌线粒体结构、功能、自噬作用、凋亡作用的改变与干预方面的研究进展做了总结论述。     

四逆汤改善缺血心肌能量代谢的作用及其机制探讨

目的：探讨四逆汤改善缺血心肌能量代谢的作用及其机制。方法：垂体后叶素性小鼠心肌缺血模型，四逆汤（浓度１０３ｇ生药／Ｌ）灌胃，剂量０１ｍＬ／２０ｇｗｔ·ｄ－１，心肌超微结构用电镜观察分析，心肌ＡＴＰ含量用高效液相色谱法测定，乳酸浓度用常规生化方法测定。结果：与缺血组相比，四逆汤组缺血心肌线粒体损伤显著减轻（Ｐ＜００５），糖原消耗显著减少（Ｐ＜００５），乳酸浓度显著下降（Ｐ＜００５），心肌营养血流量显著上升（Ｐ＜００１），氧自由基浓度显著降低（Ｐ＜００１）。结论：四逆汤具有显著改善缺血心肌能量代谢的作用，该作用与其增加心肌供血和清除氧自由基有关     

缺氧对大鼠心肌线粒体能量代谢和腺苷酸转位酶活性的影响

目的： 探讨高原低压缺氧暴露过程中大鼠心肌能量代谢及腺苷酸转位酶活性变化特点。 方法： 雄性Wistar大鼠随机分为正常对照组、缺氧1 d组、5 d组、15 d组和30 d组。缺氧组于模拟海拔 5 000 m高原低压舱内连续缺氧23 h/d。提取心室肌线粒体，Clark氧电极法测定线粒体氧化呼吸活性；HPLC法测量线粒体内腺苷酸含量；［3H］-ADP掺入法测量线粒体ANT转运活性。 结果： 大鼠经缺氧1 d、5 d、15d 后， ST3和RCR显著降低，缺氧30 d时ST3仍显著低于对照组， ST4在缺氧1 d、5 d、15 d时显著升高，缺氧30 d时降低，RCR在30 d时接近正常。缺氧1 d和5 d心肌线粒体ATP含量、ANT活性明显下降，缺氧15 d时接近正常，缺氧30 d时则再次降低。 结论： 缺氧对心肌线粒体氧化呼吸功能的抑制是导致线粒体内ATP含量下降的主要原因。缺氧过程中ANT活性与线粒体内ATP含量成协调变化。     

缺血性心衰心肌能量代谢变化与心功能关系的研究

心肌能量代谢变化是慢性心力衰竭的发病机制中的一个重要因素。了解心衰时心肌内能量物质磷酸腺苷酸和线粒体呼吸功能的变化规律，为揭示心衰的发病机制提供实验依据。方法将５０只雄性大鼠（２５０～３００ｇ），完全结扎左侧冠状动脉的起始部，饲养２～６周后，从左侧颈...     

缺血／再灌注对大鼠心肌线粒体电子传递与质子泵出偶联的影响

本实验采用Ｌａｎｇｅｎｄｏｒｆｆ灌流装置造成大鼠心肌缺血／再灌模型，用差速离心法分离线粒体，用Ｃｌａｒｋ氧电极测定ＲＣＲ，ＡＤＰ／Ｏ，用铁氰化钾脉冲法测定了呼吸链电子传递及质子泵出初速度。结果表明，Ｈ＾＋／２ｅ在缺血时与对照比无显著差异，而再灌组显著低于对照，Ｈ＾＋／２ｅ下降早于ＡＤＰ／Ｏ下降。ＲＣＲ、ＡＤＰ／Ｏ在缺血早期及再灌时显著高于对照。     

电针足三里减轻脓毒症模型大鼠心肌损伤的作用机制

背景:既往研究发现针刺足三里可减轻脓毒症大鼠心肌受损程度,其机制研究尚少.目的:探讨电针足三里对脓毒症大鼠心肌损伤的影响及其可能机制.方法:将48只SD大鼠随机均分成对照组、模型组、足三里组、非经非穴组,每组12只.除对照组外采用盲肠结扎穿孔术构造脓毒症大鼠心肌损伤动物模型,对照组仅开腹游离盲肠不进行盲肠穿孔结扎.于造...     

线粒体动力学在脓毒症心肌病中的研究进展

脓毒症心肌病为脓毒症的严重并发症之一,其确切病理机制尚不完全清楚.线粒体分裂-融合的动态过程称之为线粒体动力学,由一系列线粒体动力学相关蛋白调控.近年来,大量研究表明线粒体分裂-融合失衡可诱发各种心脏疾病,包括脓毒症心肌损害.目前对脓毒症心肌病尚无特异性治疗,心肌线粒体功能障碍与脓毒症心肌损害关系密切,调节线粒体动力学有望成为其干预的新靶点.     

AMPK通过增强心肌脂肪酸氧化抑制大鼠心肌肥厚

目的： 探讨单磷酸腺苷（AMP）激活的蛋白激酶（AMPK）对心肌肥厚的影响及可能涉及的作用机制。方法： 通过对大鼠行腹主动脉缩窄术（TAC）引起压力负荷增加，造成心肌肥厚的模型。术后24 h起经皮下注射AMPK的特异性激活剂AICAR(0.5 mg·kg-1·d-1)直至术后7周。处死动物前，对大鼠进行超声心动学指标的检测和血清游离脂肪酸浓度测定；处死动物，取心脏称重后计算心脏重/体重比值，测量心肌细胞的平均直径、心肌中的游离脂肪酸含量、过氧化体增殖物激活型受体α（PPARα）和肉碱棕榈酰转移酶（CPT-I）的mRNA表达。结果： （1）心肌肥厚+AICAR组大鼠的心脏重/体重比值、心肌细胞平均直径、血清及心肌中游离脂肪酸的浓度明显低于心肌肥厚对照组；（2）心肌肥厚+AICAR组大鼠心肌PPARα及CPT-I的mRNA表达明显高于心肌肥厚对照组；(3) 心肌肥厚+AICAR组大鼠心脏超声心动学指标：左室后壁舒张末期厚度、左室舒张、收缩末期内径 (PWT, LVDD, LVSD) 低于心肌肥厚对照组，左室短轴缩短率 (FS%) 则高于心肌肥厚对照组。结论： 活化的AMPK可能通过增强心肌脂肪酸氧化从而抑制压力负荷增加引起的心肌肥厚。     

重编程为心肌细胞过程中的能量代谢的研究进展

急性心肌梗死的发病率逐年上升,通过重编程细胞移植,可以促进梗死区心肌细胞再生、防治心室重构和改善心功能.但重编程效率低下,如何提高重编程的效率是目前研究的难点.代谢与细胞生命过程密切相关,心肌利用能量代谢的形式维持心脏内环境稳定和组织结构更新的物质基础,线粒体动力学参与调节能量代谢.但心肌细胞直接重编程过程中代谢机制尚未清楚.     

心肌脂肪酸氧化酶的基因调控机制及PPARα的作用

心肌是耗能最多的组织之一。在胚胎时期哺乳动物心肌处于相对缺氧的环境 ,以葡萄糖及丙酮酸作为主要的能源物质 ,出生后迅速转为依赖脂肪酸氧化。这一代谢模式的转化虽然以增加耗氧量为代价 ,但可为心肌提供大量的ＡＴＰ。正常心肌能量的70 %来源于脂肪酸的氧化 ,在饥饿、运动时脂肪酸的动员更多。因此 ,线粒体脂肪酸的 β氧化对维持心肌能量代谢及泵功能具有重要意义。脂肪酸的β氧化具有精密的调控机制[1] ,其中涉及各种相关的酶。过氧化物酶体增殖物激活受体α(ＰＰＡＲα)对心肌脂肪酸氧化酶的基因表达具有重要的调节功能 ,能促进心肌细…     

Effect of helium-neon laser radiation on myocardial energy metabolism

Department of Medico-Biological Research, Research Institute of Laser Surgery, Ministry of Health of the USSR, Moscow. Laboratory of Morphology, N. I. Pirogov Second Moscow Medical Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR V. V. Kupriyanov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 111, No. 3, pp. 302–305, March, 1991.     

一氧化氦与脂肪细胞能量代谢

脂肪组织在维持机体的能量代谢平衡和糖、脂代谢稳态中起着重要作用。脂肪细胞合成、释放的一氧化氮(n itric oxide,NO)通过影响线粒体生物合成、脂肪细胞分化以及脂肪分解等,参与能量代谢的调节。NO生成异常可导致能量代谢紊乱甚至肥胖和胰岛素抵抗,后者是冠心病、高血压、2型糖尿病及高脂血症等多种疾病共同的病理基础。深入研究NO对脂肪细胞能量代谢的调控及其机制,可为探讨上述疾病的发生机理和防治措施提供新的思路。     

Effect of the assisted circulation on myocardial ultrastructure

The effect of a method of assisted circulation (counterpulsation) on the ultrastructure of the myocardium was studied in dogs. Electron microscopy revealed a sharp increase in the glycogen content in the heart muscle cells, mitochondria with a highly osmophilic, finely granular matrix, and high pinocytotic activity of the capillary endothelial cells. The results are evidence of metabolic changes in the myocardium and, in particular, that the myocardial muscle cells are functioning at a lower energy level. The changes discovered in the myocardial ultrastructure evidently account for the beneficial therapeutic effect of the method.Institute of Transplantation of Organs and Tissues, Ministry of Health of the USSR. Department of Pathological Anatomy, Moscow Medical Stomatological Institute. (Presented by Academician of the Academy of Medical Sciences of the USSR B. V. Petrovskii.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 82, No. 12, pp. 1497–1499, December, 1976.     

Coupling energy metabolism with a mechanism to support brain-derived neurotrophic factor-mediated synaptic plasticity

Synaptic plasticity and behaviors are likely dependent on the capacity of neurons to meet the energy demands imposed by neuronal activity. We used physical activity, a paradigm intrinsically associated with energy consumption/expenditure and cognitive enhancement, to study how energy metabolism interacts with the substrates for neuroplasticity. We found that in an area critical for learning and memory, the hippocampus, exercise modified aspects of energy metabolism by decreasing oxidative stress and increasing the levels of cytochrome c oxidase-II, a specific component of mitochondrial machinery. We infused 1,25-dihydroxyvitamin D3, a modulator of energy metabolism, directly into the hippocampus during 3 days of voluntary wheel running and measured its effects on brain-derived neurotrophic factor-mediated synaptic plasticity. Brain-derived neurotrophic factor is a central player for the effects of exercise on synaptic and cognitive plasticity. We found that 25-dihydroxyvitamin D3 decreased exercise-induced brain-derived neurotrophic factor but had no significant effect on neurotrophin-3 levels, thereby suggesting a level of specificity for brain-derived neurotrophic factor in the hippocampus. 25-Dihydroxyvitamin D3 injection also abolished the effects of exercise on the consummate end-products of brain-derived neurotrophic factor action, i.e. cyclic AMP response element-binding protein and synapsin I, and modulated phosphorylated calmodulin protein kinase II, a signal transduction cascade downstream to brain-derived neurotrophic factor action that is important for learning and memory. We also found that exercise significantly increased the expression of the mitochondrial uncoupling protein 2, an energy-balancing factor concerned with ATP production and free radical management. Our results reveal a fundamental mechanism by which key elements of energy metabolism may modulate the substrates of hippocampal synaptic plasticity.     

丹参联合黄芪对糖尿病肾病大鼠肾脏线粒体呼吸及能量代谢的影响

目的:探讨丹参联合黄芪对糖尿病肾病(DN)大鼠肾脏功能及线粒体呼吸和能量代谢的影响。方法:选择健康SD大鼠,使用链脲佐菌素制作DN大鼠模型,按随机数字表法分为DN模型组(DN组)、丹参注射液干预组(丹参组)、黄芪注射液干预组(黄芪组)、丹参联合黄芪注射液干预组(联合组)和正常对照组(对照组),每组各8只。丹参组加予丹参注射液灌胃,黄芪组加予黄芪注射液灌胃,联合组加予丹参联合注射液灌胃,正常组和DN组同时给予等量的生理盐水,连续喂养6周。检测空腹血糖、血尿素氮、血清肌酐、24小时尿量及尿蛋白定量,留取肾组织,高效液相色谱法检测ATP、ADP、AMP,提取线粒体,氧电极法检测线粒体3态呼吸速率(T3)、4态呼吸速率(T4)和呼吸控制率(RCR)。结果:与DN组大鼠比较,丹参组、黄芪组和联合组大鼠的血糖水平、血尿素氮、血清肌酐、尿蛋白定量下降,24 h尿量增加,肾脏组织线粒体T3和RCR升高,ATP、ADP含量增加,P均<0.05。但联合组与丹参组和黄芪组对比,各项指标无显著差异。结论:丹参和黄芪单用及联合可能通过改善DN大鼠肾脏线粒体呼吸功能及能量代谢,改善DN大鼠肾脏的功能。丹参联合黄芪组较单纯丹参或单纯黄芪无显著优势。     

Combined effects of hypoxia and endurance training on lipid metabolism in rat skeletal muscle

Aim: To determine whether endurance training can counterbalance the negative effects of hypoxia on mitochondrial phosphorylation and expression of the long chain mitochondrial fatty acid transporter muscle carnitine palmitoyl transferase 1 (mCPT‐1). Methods: Male Wistar rats were exposed either to hypobaric hypoxia (at a simulated altitude of ≈4000 m, PIO₂ ≈ 90 mmHg) or to normoxia (sea level) for 5 weeks. In each environment, rats were randomly assigned to two groups. The trained group went through a 5‐week endurance training programme. The control group remained sedentary for the same time period. Muscle fatty acid oxidation capacity was evaluated after the 5‐week period on isolated mitochondria prepared from quadriceps muscles with the use of palmitoylcarnitine or pamitoylCoA + carnitine. Results: Chronic hypoxia decreased basal (V₀, ?31% with pamitoylCoA + carnitine and ?21% with palmitoylcarnitine, P < 0.05) and maximal (V_max, ?31% with pamitoylCoA + carnitine, P < 0.05) respiration rates, hydroxyacylCoA dehydrogenase activity (?48%, P < 0.05), mCPT‐1 activity index (?34%, P < 0.05) and mCPT‐1 protein content (?34%, P < 0.05). Five weeks of endurance training in hypoxia brought V₀, mCPT‐1 activity index and mCPT‐1 protein content values back to sedentary normoxic levels. Moreover, in the group trained in hypoxia, V_max reached a higher level than in the group that maintained a sedentary lifestyle in normoxia (24.2 nmol O₂· min^?1 · mg^?1 for hypoxic training vs. 19.9 nmol O₂ · min^?1 · mg^?1 for normoxic sedentarity, P < 0.05). Conclusion: Endurance training can attenuate chronic hypoxia‐induced impairments in mitochondrial fatty acid oxidation. This training effect seems mostly mediated by mCPT‐1 activity rather than by mCPT‐1 content.     

Cardioprotective effects of trimetazidine and a combination of succinic and malic acids in acute myocardial ischemia

A mixture of mitochondrial substrates of succinic and malic acids more effectively than antihypoxant trimetazidine prevented functional and metabolic disorders in rat myocardium during acute ischemia: reduces T wave amplitude, QT interval, number and duration of arrhythmias, and restores oxidation-phosphorylation coupling. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 8, pp. 183–187, August, 2008