Kuzuya T, Fuji H, Hoshida S, Nishida M, Goshima K, Hori M, Kamada T, Tada M
Department of Pathophysiology, Osaka University School of Medicine, Japan.
Free Radic Biol Med. 1994 Dec;17(6):501-10. doi: 10.1016/0891-5849(94)90089-2.
Growing evidence suggests that free radicals derived from polymorphonuclear leukocytes (PMNs) play an important role in myocardial ischemia-reperfusion injury. To elucidate the cellular mechanism by which activated PMNs exacerbate ischemic myocardial damage, we investigated the extent of cell injury, assessed by the morphological deterioration, free radical generation, and lipid peroxidation in mouse embryo myocardial cells coincubated with activated PMNs. The generation of PMN-derived free radicals was related to the extent of myocardial cell injury. When myocardial cell sheets were subjected to hypoxia and glucose-free media, myocardial cells were injured (cristalysis in the mitochondria and disruption of the sarcolemma) after adding various PMN activators, and the injury extended to the adjacent cells. Chemiluminescent emission and production of thiobarbituric acid-reactive substances in the coincubated cells increased markedly compared with myocardial cells or PMNs alone. The augmented lipid peroxidation coincided with the progression of myocardial cell injury. Catalase inhibited the myocardial cell injury by 52%, the chemiluminescence by 46%, and lipid peroxidation by 50%, whereas superoxide dismutase exhibited less pronounced inhibition. These results indicate that a chain reaction of lipid peroxidation in myocardial cells induced by PMN-derived free radicals closely correlates with membrane damage and contributes to the propagation of irreversible myocardial cell damage.
越来越多的证据表明，多形核白细胞（PMN）产生的自由基在心肌缺血再灌注损伤中起重要作用。为了阐明活化的PMN加重缺血性心肌损伤的细胞机制，我们研究了与活化的PMN共同孵育的小鼠胚胎心肌细胞的细胞损伤程度，通过形态学恶化、自由基生成和脂质过氧化来评估。PMN衍生自由基的生成与心肌细胞损伤程度相关。当心肌细胞片暴露于缺氧和无糖培养基时，在添加各种PMN激活剂后，心肌细胞受到损伤（线粒体嵴溶解和肌膜破坏），并且损伤扩展到相邻细胞。与单独的心肌细胞或PMN相比，共同孵育细胞中的化学发光发射和硫代巴比妥酸反应性物质的产生显著增加。脂质过氧化的增强与心肌细胞损伤的进展一致。过氧化氢酶抑制心肌细胞损伤52%，化学发光46%，脂质过氧化50%，而超氧化物歧化酶的抑制作用不明显。这些结果表明，PMN衍生自由基诱导的心肌细胞脂质过氧化链式反应与膜损伤密切相关，并导致不可逆心肌细胞损伤的传播。
