摘要
目的研究甲基苯丙胺(MA)对大鼠心肌线粒体结构及Cytochrome C、Caspase-3、Caspase-9 mRNA的影响作用。方法采用MA(3 mg/kg)急、慢性体内给药方式染毒大鼠,电子显微镜观察心肌细胞线粒体结构,RT-PCR检测心肌Cytochrome C、Caspase-3、Caspase-9 mRNA表达水平。结果急性MA中毒引起大鼠心肌线粒体轻度肿胀及Caspase-9 mRNA表达水平的上升,慢性MA中毒导致心肌细胞线粒体结构严重损伤,明显上调Caspase-3、Caspase-9 mRNA表达水平,而急、慢性MA中毒对大鼠Cytochrome C mRNA表达水平无明显影响。结论长期反复使用MA可破坏心肌线粒体结构,上调Caspase-9、Caspase-3 mRNA表达水平。线粒体诱导的凋亡通路可能是MA诱导心肌损伤的重要机制之一。
Objective To study the influence of methamphetamine(MA) on the structure of mitochondria and the expression of Cytochrome C, Caspase-3, Caspase-9 mRNA of myocardium in rats and to investigate the mechanism of myocardial damage induced by methamphetamine. Methods The toxic effects of acute and chronic administration of methampbetamine (3 mg/kg) were studied in rats. Myocardial mitochondria were examined with electron microscopy. Expression of myocardial Cytochrome C, Caspase-3, and Caspase-9 mRNA was examined by RT-PCR. Results Acute toxicity of methamphetamine led to mild swell of mitochondria and increased expression of Caspase-9 mRNA in rat heart. Chronic toxicity of methamphetamine led to severe swell and degeneration of mitochondria and increased markedly expression of Caspase-3 and Caspase-9 mRNA in rat heart. There had no obvious change of expression of cytochrome C mRNA in rats with acute and chronic administration of methamphetamine. Conclusion Chronic methamphetamine use may destroy the structure of mitochondria and increase the levels of expression of Caspase-9, Caspase-3 mRNA in heart. The mitochondria-initiated apoptosis pathway could be one of important mechanism of myocardial damage induced by methamphetamine.
出处
《毒理学杂志》
CAS
CSCD
北大核心
2008年第5期349-352,共4页
Journal of Toxicology
基金
湖北省卫生厅科研基金项目(项目编号JX3B55)