Antioxidants attenuate myocyte apoptosis in the remote non-infarcted myocardium following large myocardial infarction

被引:74
|
作者
Oskarsson, HJ
Coppey, L
Weiss, RM
Li, WG
机构
[1] Univ Iowa, Dept Internal Med, Div Cardiovasc Dis, Iowa City, IA 52242 USA
[2] Vet Adm Med Ctr, Iowa City, IA 52242 USA
关键词
apoptosis; free radicals; heart failure;
D O I
10.1016/S0008-6363(99)00400-9
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective: Increased oxidative stress and myocyte apoptosis co-exist in the remote non-infarcted myocardium (RM) following a large myocardial infarction. We proposed that these phenomena are causally related. Methods and results: On day 3 after induction of myocardial infarction, Sprague-Dawley rats were randomized to receive probucol and pyrrolidine dithiocarbamate (MI-T), or vehicle only (MI) for 7 weeks. Control rats (C) received vehicle. At 7 weeks, lipidperoxidation within the RM was assessed by measuring thiobarbituric acid reactive substances, which were significantly increased in MI vs. C, while MI-T was not different from C. There was a significant increase in cardiac myocytes positive for in situ TdT-UTP nick-end labeling within the RM in MI vs. C, which was inhibited in MI-T. Furthermore, internucleosomal DNA fragmentation was clearly demonstrated on agarose gels from RM in the MI group, while it was much less apparent on gels from RM in the C and MI-T groups. Western blot analysis showed a significant increase in p53, Bar and caspase-3 protein expression within the RM of MI vs. C, all of which were inhibited in the MI-T group. Furthermore, then was evidence for an increase in caspase-3 activity within the RM from MI vs. C, which was normalized in the MI-T group. Conclusions: Long-term treatment with the antioxidants probucol and pyrrolidine dithiocarbamate attenuates oxidative stress, myocyte apoptosis, caspase-3 like activity and the expression of p53, bar and caspase-3 within RM in rats after a large myocardial infarction. (C) 2000 Elsevier Science B.V. All lights reserved.
引用
收藏
页码:679 / 687
页数:9
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