二氧化硫对心肌细胞线粒体损伤的分子机制探讨

Molecular mechanism of sulfur dioxide on rat myocardial cell mitochondria damage

采用Wistar大鼠作为模型进行整体动物动式吸入染毒,在大鼠吸入不同浓度SO2(0、7、14、28 mg·m-3,7 d,6 h·d-1)后,采用荧光定量PCR技术检测心肌细胞中由线粒体DNA(mtDNA)编码的细胞色素C氧化酶和ATP合酶的几种亚基及调控线粒体呼吸链组分的核转录因子PGC-1α、NRF-1和mtTFA的mRNA水平.结果发现,SO2染毒后,随着SO2浓度的升高,大鼠心肌中细胞色素C氧化酶3种亚基(CO1、CO2、CO3)和ATP合酶两种亚基(ATP6&8)mRNA表达水平均显著降低,调控基因PGC-1α、NRF1和mtTFA的mRNA表达水平也显著降低.提示大鼠吸入SO2后,可能通过降低心肌中PGC-1α表达,影响其与NRF1结合及对mtTFA调控,进一步抑制线粒体基因组的转录,最终可能使大鼠心肌线粒体的氧化磷酸化功能受损,进而引起心衰等心血管疾病.

Male Wistar rats were housed in exposure chambers and treated with 0,7,14,and 28 mg·m-3SO 2 for 6 h·d-1for 7 days. Analyses of mitochondrial oxidative phosphorylation complex and three mitochondrial transcript factors transcription,including NRF1,mtTFA and PGC-1α,were performed by real time PCR. Our results showed that mRNA expression of CO1,CO2,CO3,and ATP6 & 8 significantly decreased in rats after SO2 exposure. Moreover,it was accompanied by depression of three transcript factors. It was indicated that SO2 inhalation induced rat myocardial cell mitochondrial dysfunction might be related to the PGC-1α pathway,and the diminished transcriptional levels of electron transport chain subunits. It might cause the damage of rat myocardial cell mitochondrial oxidative phosphorylation function and even some cardiovascular disease,such as heart failure.