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抗硝基化治疗对硫氧还蛋白活性及缺血/再灌注后心肌细胞凋亡的影响(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第3期
页码:
253-258
栏目:
出版日期:
2008-05-20

文章信息/Info

Title:
Effects of antinitration on thioredoxin activation and postischemic myocardial apoptosis
作者:
张航向1; 2; 臧益民2; 李树壮2; 高峰2; 马新亮2
第四军医大学： 1.西京医院老年病一科，2.基础部生理学教研室，陕西 西安 710032
Author(s):
ZHANG Hangxiang1; 2;  ZANG Yimin2;  LI Shuzhuang2;  GAO Feng2;  MA Xinliang2
1.Department of Geriatrics, Xijing Hospital, 2.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China
关键词:
凋亡; 硫氧还蛋白; 蛋白质硝基化; 心肌缺血/再灌注
Keywords:
apoptosis;  thioredoxin;  protein nitration;  ischemia/reperfusion
分类号:
R542.2
DOI:
-
文献标识码:
A
摘要:
目的: 硫氧还蛋白（Trx）是一个重要的抗凋亡分子，硝基化可降低其活性，我们观察抗硝基化治疗对Trx活性的影响。方法：C57/B16小鼠心肌缺血30 min，在再灌注前10 min腹腔注射FP15（ONOO清除剂，5 mg/kg）。结果：在缺血/再灌注组，缺血区心肌组织中总一氧化氮（NO）和硝基酪氨酸含量显著增加，Trx发生了明显的硝基化且活性被抑制，Trx和ASK1的结合减低，p38 MAPK的活性升高。在灌注前10 min给予FP15治疗可以阻止硝基酪氨酸的生成\[(188±023) vs (029±014) nmol/g protein,P<001\]，Trx的硝基化降低 (519±51 vs 182±29,P<001)，Trx的活性恢复\[(098±011) vs (168±012) mol/(min·g protein),P<001\],P38 MAPK的活性减低(148±004 vs 059±010,P<001)，从而降低caspase 3活性\[(180±09) vs (77±16) μmol/(h·g protein),P<001\],减少心肌梗死范围(397%±28% vs 237%±23%,P<001) 。结论：抗硝基化治疗可以恢复Trx的活性，改善缺血/再灌注心肌的预后。
Abstract:
AIM Thioredoxin (Trx) is an important antiapoptotic molecule. Several recent studies have demonstrated that Trx activity is decreased by posttranslational nitrative modification. The present study was designed to determine whether antinitration treatment could restore thioredoxin activity. METHODS: C57/B16 mice were subjected to 30 min of myocardial ischemia and treated with either vehicle or FP15 (peroxynitrite decomposition catalyst, 5 mg/kg, ip) 10 min before reperfusion. RESULTS: In cardiac tissues obtained from ischemic/reperfused heart, total NO production and cardiac nitrotyrosine were markedly increased, significant Trx nitration was detected, Trx activity was markedly inhibited, Trx/ASK1 (apoptosis signalregulating kinase1) complex formation was abolished, and ASK1 activity was increased. Treatment with FP1510 min before reperfusion blocked nitrotyrosine production \[(188±023) nmol/g protein vs (029±014) nmol/g protein, P<001\], reduced Trx nitration(519±51 vs 182±29, P<001), restored Trx activity \[(098±011) mol/(min·g protein) vs (168±012) mol/(min·g protein), P<001\], decreased P38 MAPK activity (148±004 vs 059±010, P<001), attenuated caspase 3 activation \[(180±09) μmol/(h·g protein) vs (77±16) μmol/(h·g protein), P<001\] and reduced infarct size (397%±28% vs 237%±23%, P<001). CONCLUSION: Antinitration treatment can restore thioredoxin activity and improve the myocardial ischemia/reperfusion outcome.

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备注/Memo

备注/Memo:
收稿日期：2008-01-30.基金项目：美国国立卫生院基金课题（2R01HL-63828） 美国糖尿病协会基金课题（7-05-RA-83） 通讯作者：臧益民，教授，主要从事心血管生理研究 Email:zangym@fmmu.edu.cn 作者简介：张航向，主治医师，博士生 Email：zhanghx@fmmu.edu.cn
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