Go 6983: a fast acting protein kinase C inhibitor that attenuates myocardial ischemia/reperfusion injury.
Go 6983: a fast acting protein kinase C inhibitor that attenuates myocardial ischemia/reperfusion injury.
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Go 6983：一种速效蛋白激酶 C 抑制剂，可减轻心肌缺血/再灌注损伤。
DOI：
10.1111/j.1527-3466.2005.tb00170.x
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Weis,MargaretT
中科院分区：
文献类型：
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作者：
Young,LindonH;Balin,BrianJ;Weis,MargaretT
再灌注损伤的特征在于再灌注后5分钟内内皮释放的一氧化氮减少，白细胞-内皮相互作用增加，白细胞迁移到心肌中，产生心脏收缩功能障碍。Gö 6983是一种快速起效的脂溶性广谱蛋白激酶C抑制剂。当在再灌注开始时给药时，它可以在5分钟内恢复心脏功能并减轻与急性缺血/再灌注相关的有害作用。Gö 6983可能比其他广谱PKC抑制剂在缺血后再灌注损伤中提供更大的心脏保护作用，因为它抑制PKC β和其他四种亚型。心脏保护作用与减少白细胞超氧化物释放和增加血管组织内皮源性一氧化氮有关。人体组织的体外研究表明，Gö 6983可显著抑制先前对树花粉致敏的患者的白细胞中抗原诱导的超氧化物释放。在人体血管组织中，Gö 6983抑制细胞内Ca 2+的积累，这表明其血管扩张特性的机制。这些研究表明，Gö 6983将是一种有效的化合物，可用于器官移植和/或脑缺血的临床缺血/再灌注环境，其中抑制缺血后组织中的超氧化物释放和血管收缩将允许在再灌注期间更好地恢复器官功能。然而，考虑到Gö 6983的广谱作用，建议谨慎调整剂量方案，以确保在器官移植和/或脑缺血的情况下取得成功。
Reperfusion injury is characterized by a decrease in endothelial release of nitric oxide within 5 min after reperfusion, increased leukocyte‐endothelium interaction, and transmigration of leukocytes into the myocardium, producing cardiac contractile dysfunction. Gö 6983 is a fast acting, lipid soluble, broad spectrum protein kinase C inhibitor. When administered at the beginning of reperfusion, it can restore cardiac function within 5 min and attenuate the deleterious effects associated with acute ischemia/reperfusion. Gö 6983 may offer greater cardioprotection than other broad‐spectrum PKC inhibitors in post‐ischemic reperfusion injury because it inhibits PKCξ as well as four other isoforms. The cardioprotection is associated with decreased leukocyte superoxide release and increased endothelial derived nitric oxide from vascular tissue.In vitrostudies of human tissue showed that Gö 6983 significantly inhibited antigen‐induced superoxide release from leukocytes of patients previously sensitized to tree pollen. In human vascular tissue, Gö 6983 inhibited intracellular Ca2+accumulation, suggesting a mechanism for its vasodilator properties. These studies suggest that Gö 6983 would be an effective compound to use in a clinical ischemia/reperfusion setting of organ transplantation and/or cerebral ischemia where inhibiting superoxide release and vasoconstriction in postischemic tissues would allow for better restoration of organ function during reperfusion. However, given the broad‐spectrum action of Gö 6983, careful titration of the dose regimen would be recommended to ensure a successful outcome in the setting of organ transplantation and/or cerebral ischemia.