Zhang Yan-Mei, Shi Gang-Gang, Tang Zhao, Zheng Jin-Hong, Li Wei-Qiu, Guo Fu-Xiao, Jia Qiang-Yong
Department of Pharmacology, Shantou University Medical College, Shantou 515041, China.
Acta Biochim Biophys Sin (Shanghai). 2006 Jun;38(6):435-41. doi: 10.1111/j.1745-7270.2006.00180.x.
We have previously shown that N-n-butyl haloperidol iodide (F2) derived from haloperidol reduces ischemia/reperfusion-induced myocardial injury by blocking intracellular Ca2+ overload. This study tested the hypothesis that cardio-protection with F2 is associated with an attenuation in the expression of early growth response gene 1 (Egr-1). In an in vivo rat model of 60 min coronary occlusion followed by 180 min of reperfusion, treatment with F2 significantly reduced myocardial injury evidenced by the reduction in release of plasma creatine kinase, myocardial creatine kinase isoenzyme and lactate dehydrogenase. In cultured neonatal rat cardiomyocytes of hypoxia for 3 h and reoxygenation for 1 h, F2 treatment attenuated necrotic and apoptotic cell death, as demonstrated by electron microscopy. Concomitant with cardio-protection by F2, the increased expression levels of Egr-1 mRNA and protein were significantly reduced in myocardial tissue and cultured cardiomyocytes as detected by reverse transcription-polymerase chain reaction, immunohistochemistry and immunocytochemistry. In conclusion, these results suggest that the protective effect of F2 on ischemia/reperfusion- or hypoxia/reoxygenation-induced myocardial injury might be partly mediated by downregulating Egr-1 expression.
我们之前已经表明，源自氟哌啶醇的N-正丁基氟哌啶醇碘化物（F2）通过阻止细胞内Ca2+过载来减轻缺血/再灌注诱导的心肌损伤。本研究检验了以下假设：F2的心脏保护作用与早期生长反应基因1（Egr-1）表达的减弱有关。在一个60分钟冠状动脉闭塞随后180分钟再灌注的体内大鼠模型中，F2治疗显著减轻了心肌损伤，这可通过血浆肌酸激酶、心肌肌酸激酶同工酶和乳酸脱氢酶释放的减少来证明。在培养的新生大鼠心肌细胞中进行3小时缺氧和1小时复氧处理，电子显微镜显示F2治疗减轻了坏死和凋亡性细胞死亡。与F2的心脏保护作用相伴，通过逆转录-聚合酶链反应、免疫组织化学和免疫细胞化学检测发现，心肌组织和培养的心肌细胞中Egr-1 mRNA和蛋白质的表达水平升高显著降低。总之，这些结果表明，F2对缺血/再灌注或缺氧/复氧诱导的心肌损伤的保护作用可能部分是通过下调Egr-1表达来介导的。
