【摘要】 百草枯（paraquat,PQ）是目前农业生产上使用较为广泛的除草剂,PQ毒性极大,能造成人和动物多器官损伤。因肝脏是主要的受损器官之一,故以肝细胞L-O2为研究对象,探讨PQ急性暴露对肝细胞产生的毒理影响。结果显示在40!640μmol·L^-1暴露浓度下作用24 h,PQ显著抑制肝细胞L-O2的增殖活性（P<0.01）,半抑制浓度（IC50）为263.2μmol·L^-1。将肝细胞L-O2暴露于不同浓度的PQ(60、120、180和250μmol·L^-1),作用24 h后,与对照组相比,PQ暴露组的活性氧（ROS）累积和细胞凋亡率都表现出明显的浓度依赖性升高（P<0.01; P<0.05）,细胞周期阻滞在S期。Western blot结果显示,除60μmol·L^-1外的其他暴露组中活化的胱天蛋白酶9（caspase-9）表达显著上调,Bax和Bcl-2的比值显著增大,提示细胞凋亡机制可能与内源性线粒体通路的激活有关。此外,碳酸酐酶9（CA9） mRNA表达显著升高,提示PQ暴露下可能引起酸性代谢产物出现,对细胞产生酸毒害,但其内在的机制还需进一步研究。更多还原

【Abstract】 Paraquat（PQ） is one of the most widely used herbicides,but with ultrahigh toxicity.Its toxic effect was suggested to be related to the effect of oxidation-responsive stress,leading to multi-organ dysfunctions.As liver is the most important detoxification organ,here we reported the toxicological effects of PQ on L-O2 hepatocytes when it was acutely exposed to PQ.Our results showed that PQ was highly toxic to L-O2 hepatocytes with IC50 of 263.2 μmol·L^-1 for 24 h（P<0.01）.When L-O2 hepatocytes were exposed to PQ of different concentrations(60,120,180,250μmol·L^-1) for 24 h,the concentration-dependent increase of ROS accumulation and apoptosis rate of L-O2 hepato-cytes were observed,compared to the control group（with P<0.01,P<0.05,respectively）.The cell cycle was blocked in S phase.Further mechanistic studies were conducted on the toxicity and the apoptotic pathways.The abnormal high level of the activated caspase-9 and the ratio of Bax to Bcl-2 might indicate that an endogenous mitochondrial apoptosis could be responsible for the increased apoptosis rate of L-O2,and the distinct mRNA relative expression of carbonic anhydrase 9（CA9） indicated the acidic toxicity inside the cells,but it is necessary to study further.更多还原