M40403保护作用,选择性超氧化物歧化酶模拟物,在心肌缺血和再灌注损伤体内。

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Masini E, Cuzzocrea年代,Mazzon E,现在C, Mannaioni PF, Salvemini D

M40403保护作用,选择性超氧化物歧化酶模拟物,在心肌缺血和再灌注损伤体内。

Br J杂志。2002年7月,136(6):905 - 17所示。

PubMed ID

12110615 (在PubMed

]

文摘

1。心肌损伤引起的缺血和再灌注来自多个致病事件,包括内皮损伤,中性粒细胞外渗到组织中,肥大细胞激活,和细胞膜脂质过氧化反应。这些事件是紧随其后的是心肌细胞改变最终导致细胞坏死。一个增强活性氧的形成是被广泛接受的刺激组织破坏和心脏衰竭。2。在这项研究中,我们调查了心血管效应的M40403心肌ischaemia-reperfusion受伤。M40403低分子量,合成含有锰超氧化物歧化酶模拟(SODm)选择性地清除超氧化物阴离子。只是在老鼠的心脏体内诱导切断左前降枝冠状动脉。三十分钟的诱导缺血后,结扎切除和再灌注允许发生至少60分钟。M40403(0.1 1毫克公斤(1))静脉注射局部贫血前15分钟。3所示。 The results obtained in this study showed that M40403 significantly reduced the extent of myocardial damage, mast cell degranulation and the incidence of ventricular arrhythmias. Furthermore, M40403 significantly attenuated, in a dose-dependent manner, neutrophil infiltration in the myocardium as well as the associated induction of lipid peroxidation. Calcium overload seen post-reperfusion of the ischaemic myocardium was also reduced by M40403. 4. Immunohistochemical analysis for nitrotyrosine revealed a positive staining in cardiac tissue taken after reperfusion: this was attenuated by M40403. Moreover reperfused cardiac tissue sections showed positive staining for P-selectin and for anti-intercellular adhesion molecule (ICAM-1) in the vascular endothelial cells. M40403 treatment markedly reduced the intensity and degree of P-selectin and ICAM-1 in these tissues. No staining for nitrotyrosine, P-selectin or ICAM-1 was found in cardiac tissue taken at the end of the ischaemic period. 5. Overall, M40403 treatment reduced the morphological signs of myocardial cell injury and significantly improved survival. 6. Taken together, these results clearly indicate that M40403 treatment exerts a protective effect against ischaemia-reperfusion-induced myocardial injury, supporting a key role for superoxide anion in reperfusion injuries. This suggests that synthetic enzymes of SOD such as M40403, offer a novel therapeutic approach for the treatment of ischaemic heart disease where superoxide anion plays a dominant role.

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M40403