超氧化物歧化酶模拟M40403改善内皮功能在载脂蛋白(E)不足的老鼠。

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江F,郭Y, Salvemini D,除尘GJ

超氧化物歧化酶模拟M40403改善内皮功能在载脂蛋白(E)不足的老鼠。

Br J杂志。2003年7月,139 (6):1127 - 34。

PubMed ID

12871831 (在PubMed

]

文摘

1。生产过剩的超氧化物阴离子血管壁导致内皮功能障碍在血管疾病。superoxide-generating降低beta-nicotinamide腺嘌呤二核苷酸磷酸(NADPH氧化酶)最近被确认为血管组织中氧化自由基的主要来源。我们研究了合成的影响manganese-containing超氧化物歧化酶(SOD)模拟,M40403, NADPH oxidase-dependent过氧化物生成和内皮功能障碍。2。在大鼠主动脉平滑肌细胞,NADPH(100微米)明显刺激过氧化物生产检测到lucigenin(5微M)之二化学发光。M40403降低NADPH oxidase-dependent过氧化物浓度的方式生产,与集成电路(50)31.6微m .相比之下,原生铜/锌SOD (300 U ml(1)没有影响。血管紧张素ⅱ(100海里)NADPH氧化酶活性增加了70%,和治疗M40403(10微米)减少增加超氧化物控制水平。3所示。aortae从载脂蛋白(E)缺乏小鼠(apoE(0))高脂血症和动脉粥样硬化,过氧化物生产在很大程度上是来自NADPH氧化酶。 The attenuation of endothelial nitric oxide vasodilator function parallels the increase in vascular superoxide production at different stages of the disease. Acute incubation of such aortic rings with M40403 significantly suppressed superoxide production and improved endothelium-dependent vasorelaxation to a level comparable to that in wildtype control mice. 4. In summary, the cell-permeable SOD mimetic M40403 was found to reverse endothelial dysfunction in apoE(0) aorta ex vivo by decreasing NADPH oxidase-dependent superoxide levels. The advantages of synthetic SOD mimetics over the native Cu/Zn SOD enzyme, such as greater cell permeability and stability, confer significant therapeutic potential in vascular disease.

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药物

M40403