Kajstura J, Liu Y, Baldini A, Li B, Olivetti G, Leri A, Anversa P
Department of Medicine, New York Medical College, Valhalla 10595, USA.
Am J Cardiol. 1998 Sep 3;82(5A):30K-41K. doi: 10.1016/s0002-9149(98)00535-9.
The purpose of this study was to determine whether coronary artery narrowing was associated with the activation of necrotic and apoptotic myocyte cell death in the myocardium and whether these 2 forms of cell death were restricted to the left ventricle, or involved the other portions of the heart. Coronary artery narrowing was surgically induced in rats, and the animals were killed from 45 minutes to 12 days after surgery. Myocyte apoptosis was detected by the terminal deoxynucleotidyl transferase assay, confocal microscopy, and deoxyribonucleic acid (DNA) agarose gel electrophoresis. Myocyte necrosis was identified by myosin monoclonal antibody labeling of the cytoplasm. A separate group of animals was treated with trimetazidine in an attempt to interfere with tissue injury. Coronary artery narrowing was characterized by myocyte apoptosis in the left ventricle and interventricular septum, which progressively increased from 45 minutes to 6 days. However, apoptosis was not observed at 12 days. Conversely, myocyte necrosis reached its maximum value at 1 day and was still present at 12 days. This form of cell death affected not only the left ventricular free wall and interventricular septum, but also the right ventricle. Cell necrosis markedly exceeded apoptosis at all intervals. At the peak of cell death, myocyte necrosis was 52-fold and 33-fold higher than apoptosis in the left ventricle and septum. In conclusion, necrotic myocyte cell death is the prevailing form of damage produced by coronary artery narrowing, but apoptotic cell death contributes to the loss of myocytes in the ischemic heart. Trimetazidine treatment attenuated the extent of myocardial damage produced by global ischemia.
本研究的目的是确定冠状动脉狭窄是否与心肌中坏死和凋亡性心肌细胞死亡的激活相关，以及这两种细胞死亡形式是否仅限于左心室，还是涉及心脏的其他部分。通过手术诱导大鼠冠状动脉狭窄，并在术后45分钟至12天处死动物。通过末端脱氧核苷酸转移酶测定、共聚焦显微镜和脱氧核糖核酸（DNA）琼脂糖凝胶电泳检测心肌细胞凋亡。通过肌球蛋白单克隆抗体标记细胞质来鉴定心肌细胞坏死。另一组动物用曲美他嗪治疗，试图干扰组织损伤。冠状动脉狭窄的特征是左心室和室间隔中的心肌细胞凋亡，从45分钟到6天逐渐增加。然而，在12天时未观察到凋亡。相反，心肌细胞坏死在1天时达到最大值，并在12天时仍然存在。这种细胞死亡形式不仅影响左心室游离壁和室间隔，还影响右心室。在所有时间段，细胞坏死均明显超过凋亡。在细胞死亡高峰期，左心室和室间隔中的心肌细胞坏死比凋亡分别高52倍和33倍。总之，坏死性心肌细胞死亡是冠状动脉狭窄产生的主要损伤形式，但凋亡性细胞死亡导致缺血性心脏中心肌细胞的丢失。曲美他嗪治疗减轻了全脑缺血所致心肌损伤的程度。
