次血红素六肽保护心肌线粒体抗氧化损伤作用研究

DhHP-6 Protect of myocardial mitochondrial antioxidant injury

目的本文设计并合成了一个具有高活性的抗坏血酸过氧化物模拟酶-次血红素六肽,并探讨了次血红素六肽对离体心肌线粒体氧化损伤的保护作用。方法以Vc/Fe3+/MT自由基诱导损伤体系建立了离体心肌线粒体氧化损伤模型,以膜脂质过氧化产物丙二醛(MDA),线粒体膨胀度和细胞色素C氧化酶(CCO)活性为指标研究了次血红素六肽对心肌线粒体的抗氧化保护作用。结果线粒体氧化损伤模型而中MDA生成量随着时间的延长而增大,表现为532nm处光吸收值的上升;DhHP-6保护组MDA生成量程度明显降低;DhHP-6防止了线粒体的异常膨胀,使其功能得以正常发挥;CCO是呼吸链的关键酶之一,它的活性变化反映了线粒体内呼吸链的完整性,与损伤组相比,DhHP-6的加入,CCO的结构和功能得到有效地保护,酶活性明显高于损伤组。结论在大量氧化性物质存在的体系中,DhHP-6可有效地保护心肌线粒体的正常功能。DhHP-6为进一步研究线粒体氧化损伤与多种疾病的关系提供了一个有用的工具,也为开发与此相关的新药提供了一个具有潜力的先导化合物。

Objective In this paper,we design and synthesis of a high activity of ascorbate peroxidase mimic enzyme DhHP-6,and probes into the DhHP-6 on isolated cardiac mitochondrial oxidative injury. Methods In Vc/Fe3＋/MT induced free radical injury system established from in vitro myocardial mitochondrial oxidative damage model,membrane lipid peroxidation product MDA,mitochondrial swelling and CCO activity as an index of DhHP-6 on myocardial mito- chondrial antioxidant protection. Results Mitochondrial oxidative injury mode and MDA generation as time increases, performance for the 532nm absorbance value rise ; DhHP-6 protection group： MDA yield significantly lower level; Mi- tochondrial oxidative injury mode and MDA generation as time increases, performance for the 532nm absorbance value rise protection group; MDA yield significantly lower level; DhHP-6 prevents mitochondrial abnormalities in expansion, the function of the normal play; CCO is one of the key enzymes in the respiratory chain,its activity change reflecting the mitochondrial respiratoty chain integrity, and the injury group, the accession to the DhHP-6, the structure and func- tion of CCO protected effectively,the enzyme activity was significantly;.higher in injury group. Conclusion In a large number of oxidizing substances exist in the system,DhHP-6 can protect the normal function of myocardial mitochondri- a. DhHP 6 for further study of oxidative damage to mitochondrial disease with multiple relations provide a useful tool, but also for the development of associated with this drug offers a potential lead compounds.