Dhalla Naranjan S, Saini Harjot K, Tappia Paramjit S, Sethi Rajat, Mengi Sushma A, Gupta Suresh K
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, and Faculty of Medicine, University of Manitoba, Winnipeg, Canada.
J Cardiovasc Med (Hagerstown). 2007 Apr;8(4):238-50. doi: 10.2459/01.JCM.0000263489.13479.68.
Several studies have revealed varying degrees of changes in sarcoplasmic reticular and myofibrillar activities, protein content, gene expression and intracellular Ca-handling during cardiac dysfunction due to ischemia-reperfusion (I/R); however, relatively little is known about the sarcolemmal and mitochondrial alterations, as well as their mechanisms in the I/R hearts. Because I/R is associated with oxidative stress and intracellular Ca-overload, it has been indicated that changes in subcellular activities, protein content and gene expression due to I/R are related to both oxidative stress and Ca-overload. Intracellular Ca-overload appears to induce changes in subcellular activities, protein contents and gene expression (subcellular remodeling) by activation of proteases and phospholipases, as well as by affecting the genetic apparatus, whereas oxidative stress is considered to cause oxidation of functional groups of different subcellular proteins in addition to modifying the genetic machinery. Ischemic preconditioning, which is known to depress the development of both intracellular Ca-overload and oxidative stress due to I/R, was observed to attenuate the I/R-induced subcellular remodeling and improve cardiac performance. It is suggested that a combination therapy with antioxidants and interventions, which reduce the development of intracellular Ca-overload, may improve cardiac function by preventing or attenuating the occurrence of subcellular remodeling due to ischemic heart disease. It is proposed that defects in the activities of subcellular organelles may serve as underlying mechanisms for I/R-induced cardiac dysfunction under acute conditions, whereas subcellular remodeling due to alterations in gene expression may explain the impaired cardiac performance under chronic conditions of I/R.
多项研究表明，在缺血再灌注（I/R）所致心脏功能障碍期间，肌浆网和肌原纤维的活性、蛋白质含量、基因表达及细胞内钙处理存在不同程度的变化；然而，关于肌膜和线粒体的改变及其在I/R心脏中的机制，人们了解相对较少。由于I/R与氧化应激和细胞内钙超载相关，已表明I/R引起的亚细胞活性、蛋白质含量和基因表达变化与氧化应激和钙超载均有关。细胞内钙超载似乎通过激活蛋白酶和磷脂酶以及影响遗传机制来诱导亚细胞活性、蛋白质含量和基因表达的变化（亚细胞重塑），而氧化应激除了改变遗传机制外，还被认为会导致不同亚细胞蛋白质功能基团的氧化。已知缺血预处理可抑制I/R所致的细胞内钙超载和氧化应激的发展，据观察其可减轻I/R诱导的亚细胞重塑并改善心脏功能。有人提出，抗氧化剂与减少细胞内钙超载发展的干预措施联合治疗，可能通过预防或减轻缺血性心脏病引起的亚细胞重塑的发生来改善心脏功能。有人提出，亚细胞器活性缺陷可能是急性情况下I/R诱导心脏功能障碍的潜在机制，而基因表达改变导致的亚细胞重塑可能解释I/R慢性情况下心脏功能受损的原因。
