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目的:探讨右旋亚丙胺(ICRF187)预防蒽环类所致心脏毒性的药理学机制。方法:电子顺磁共振法(EPR)、核磁共振法(NMR)、质子相关分光术、光镜、电镜、免疫组织化学、生化反应、细胞培养及自发性高血压(SHR)小鼠模型。结果:①ICRF187置换铁蒽环类复合物中的铁,并与铁络合以抑制自由基的产生;②ICRF187减弱心脏毒性免疫效应细胞(树突状细胞,TH,TC淋巴细胞及巨噬细胞)的作用;③ICRF187阻断铁蒽环类复合物对呼吸酶(NADH细胞色素C还原酶及CaATP酶)的灭活;④ICRF187的肺保护作用。结论:ICRF187的心脏保护作用的药理学机制是多个机制相互作用、相互联系的,最主要的是自由基损伤机制。
Objective: To investigate the pharmacological mechanism of dexmethazine (ICRF187) in preventing cardiotoxicity induced by anthracyclines. Methods: Electron paramagnetic resonance (EPR), nuclear magnetic resonance (NMR), proton correlation spectroscopy, light microscopy, electron microscopy, immunohistochemistry, biochemical reactions, cell culture and spontaneous hypertension (SHR) mouse models. Results: ① ICRF187 replacement of iron anthracycline complexes in iron, and with iron complex to inhibit the generation of free radicals; ② ICRF 187 attenuated cardiotoxicity of immune effector cells (dendritic cells, TH, TC lymphocytes and Macrophages); ③ ICRF-187 block iron-anthracycline complexes of respiratory enzyme (NADH-cytochrome C reductase and CaATP enzyme) inactivation; ④ I CRF 187 of the lung protection. Conclusion: The pharmacological mechanism of ICRF-187 on cardioprotection is that many mechanisms interact with each other and the most important one is the mechanism of free radical damage.