Weng Dan, Lu Yan, Wei Yinna, Liu Ying, Shen Pingping
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China.
Toxicology. 2007 Mar 22;232(1-2):15-23. doi: 10.1016/j.tox.2006.12.010. Epub 2006 Dec 15.
Microcystin-LR (MC-LR) produced by cyanobacteria in diverse water systems is a potent specific hepatotoxin and has been documented to induce hepatocyte apoptosis and liver injury; however, the mechanisms have not been fully elucidated. In the present study, we investigated whether MC-LR stimulated ROS generation in the liver of mice and the role of ROS in the pathogenesis of MC-LR-induced liver injury in vivo. MC-LR treatment (60 microg/kg of body weight) for 12h prompted large amount of ROS generation in mice liver, upregulated the expression of Bax and Bid, caused the mitochondrial membrane potential (MMP) loss and hepatocyte apoptosis as well as liver injury. While pretreatment with antioxidants, oral administration of vitamin C (250mg/kg of body weight, dissolved in double distill water) and vitamin E (200mg/kg of body weight, dissolved in corn oil) per day for 3 days continually, significantly reduced the generation of ROS and effectively inhibited the MC-LR-induced hepatocyte apoptosis and liver injury, suggesting that ROS played a critical role in MC-LR-induced hepatocyte apoptosis and liver injury. The protective effect of vitamin C and E also suggested the potential interest in the clinical treatment of MC-LR-induced liver injury and hepatotoxicity.
蓝藻在各种水体系统中产生的微囊藻毒素-LR（MC-LR）是一种强效的特异性肝毒素，已有文献记载其可诱导肝细胞凋亡和肝损伤；然而，其机制尚未完全阐明。在本研究中，我们调查了MC-LR是否会刺激小鼠肝脏中活性氧（ROS）的产生以及ROS在MC-LR诱导的体内肝损伤发病机制中的作用。MC-LR以60微克/千克体重的剂量处理12小时，促使小鼠肝脏中大量产生ROS，上调Bax和Bid的表达，导致线粒体膜电位（MMP）丧失、肝细胞凋亡以及肝损伤。而每天连续3天用抗氧化剂进行预处理，口服维生素C（250毫克/千克体重，溶解于双蒸水中）和维生素E（200毫克/千克体重，溶解于玉米油中），可显著减少ROS的产生，并有效抑制MC-LR诱导的肝细胞凋亡和肝损伤，这表明ROS在MC-LR诱导的肝细胞凋亡和肝损伤中起关键作用。维生素C和E的保护作用也提示了其在临床治疗MC-LR诱导的肝损伤和肝毒性方面的潜在价值。
