基于氧化应激和线粒体功能障碍的伏马毒素B1诱导线虫神经毒性机制

为研究线粒体功能和氧化应激在伏马毒素B1(fumonisin B1,FB1)诱导神经毒性中的作用，以秀丽隐杆线虫为模型，对FB1处理后的线虫行为表型以及包括氧化应激和线粒体功能相关指标变化进行分析。结果表明，20～200μg/mL的FB1暴露24 h以剂量依赖方式诱导细胞色素氧化酶、超氧化物歧化酶（superoxide dismutase,SOD）和过氧化氢酶（catalase,CAT）相关基因（cyp35A2、sod-1、sod-3、ctl-2和ctl-3）的异常表达。此外，100～200μg/mL的FB1处理降低了线虫线粒体密度，并显著降低了三磷酸腺苷（adenosine triphosphate,ATP）水平和线粒体膜电位（P<0.05）。200μg/mL的FB1处理显著抑制了线虫线粒体呼吸链复合物I和Ⅴ的表达，提高了线粒体分裂基因drp-1的表达水平。相关性分析显示，氧化应激和线粒体功能相关指标的表达与线虫行为学表型具有显著相关性。综上，FB1可能通过参与线虫氧化应激、线粒体呼吸链和线粒体动力学过程诱导神经毒性。

Mechanism Investigation of Neurotoxicity of Caenorhabditis elegans Induced by Fumonaxin B1-Mediated Oxidative Stress and Mitochondrial Dysfunction

To study the role of mitochondrial function and oxidative stress in the neurotoxicity induced by fumonisin B1 (FB1), the model of Caenorhabditis elegans(C. elegans) was used. The behavioral phenotype of C. elegans treated by FB1, and the changes in indices related to oxidative stress and mitochondrial function were analyzed. The results showed that 20~200 μg/mL FB1 exposure for 24 hours induced abnormal expression of genes (cyp35A2、sod-1、sod-3、ctl-2,andctl-3) related to cytochrome oxidase, superoxide dismutase(SOD), and catalase(CAT) in a dose-dependent manner. Moreover, 100~200 μg/mL FB1 treatment reduced mitochondrial density of C. elegans and significantly decreased the levels of adenosine triphosphate (ATP) and the potential of mitochondrial membrane (P<0.05). The expression levels of mitochondrial respiratory chain complexes I and V were significantly inhibited by 200 μg/mL FB1 treatment, while the expression level of mitochondrial fission gene drp-1 was increased. Correlation analysis demonstrated a significant correlation between the expression of indices related to oxidative stress and mitochondrial function and the behavioral phenotype of C. elegans. In conclusion, FB1 may induce neurotoxicity by participating oxidative stress, mitochondrial respiratory chain, and mitochondrial dynamics in C. elegans.