Delayed protection of tetramethylpyrazine on neonatal rat cardiomyocytes subjected to anoxia-reoxygenation injury
Delayed protection of tetramethylpyrazine on neonatal rat cardiomyocytes subjected to anoxia-reoxygenation injury
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DOI：
10.1111/j.1742-7843.2007.00059.x
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Liu, Dan
中科院分区：
文献类型：
--
作者：
Chen, He-Ping;He, Ming;Liu, Dan
本研究旨在探讨川芎嗪（TMP）诱导的延迟预适应对培养乳鼠心肌细胞缺氧-复氧损伤的保护作用及其可能机制。使用不同浓度（100，200和500 μ M）的TMP对培养的新生大鼠心肌细胞进行预处理。测定细胞活力、乳酸脱氢酶释放、丙二醛生成、超氧化物歧化酶活性和谷胱甘肽过氧化物酶活性，以确定对缺氧-复氧损伤的保护作用。Western blot检测TMP预处理后24 h热休克蛋白70（Hsp 70）的表达。结果表明，TMP浓度依赖性地降低乳酸脱氢酶释放，提高细胞活力，抑制丙二醛生成，提高超氧化物歧化酶和谷胱甘肽过氧化物酶活性。此外，无论是蛋白激酶C抑制剂chelerythrine chloride或PD 98059，细胞外信号调节蛋白激酶1/2的选择性抑制剂，分别预处理取消延迟保护，并在TMP预处理后24小时的Hsp 70的表达显着增加，也被chelerythrine chloride或PD 98059抑制。这些结果表明，TMP可以诱导延迟心肌保护作用，通过激活蛋白激酶C和细胞外信号调节蛋白激酶1/2信号通路和随后的表达增加热休克蛋白70在大鼠新生心肌细胞。
The aim of this study was to investigate the cardioprotective effects and the possible mechanisms of delayed preconditioning induced by tetramethylpyrazine (TMP) in cultured neonatal rat cardiomyocytes subjected to anoxia-reoxygenation injury. Cultured neonatal rat cardiomyocytes were preconditioned using TMP at different concentrations (100, 200 and 500 mu M). Cell viability, lactate dehydrogenase release, malondialdehyde formation, superoxide dismutase activity and glutathione peroxidase activity were measured to determine the protective effects against anoxia-reoxygenation injury. The expression of heat shock protein 70 (Hsp70) was measured 24 hr after TMP preconditioning by Western blot analysis. The results showed that TMP decreased lactate dehydrogenase release, increased cell viability, suppressed malondialdehyde formation and augmented activities of superoxide dismutase and glutathione peroxidase in a concentration-dependent manner. Moreover, the delayed protection was abolished by pre-treating with either protein kinase C inhibitor chelerythrine chloride or PD98059, a selective inhibitor of extracellular signal-regulated protein kinase 1/2, respectively, and the expression of Hsp70 was significantly increased in 24 hr after TMP preconditioning that was also suppressed by chelerythrine chloride or PD98059. These results suggest that TMP can induce delayed cardioprotective effects by activation of protein kinase C and extracellular signal-regulated protein kinase 1/2 signalling pathways and subsequent increased expression of Hsp70 in rat neonatal cardiomyocytes.