血红素加氧酶1在斑马鱼低氧应激中的保护作用研究

摘要

Heme oxygenase 1 (Ho1) is the rate-limiting enzyme in the degradation of heme into biliverdin, carbon monoxide and free divalent iron. Abnormal expression of ho1 gene is associated with the development and progression of various human diseases, while functions of zebrafish Ho1 under hypoxia stress remain largely unknown. This study explored the protection role of zebrafish Ho1 during hypoxia exposure. The results showed that hypoxia significantly induced zebrafish ho1 mRNA in ZF4 cells, embryos, brain, gill, and liver but significantly decreased it in heart and kid-ney after 24h hypoxic exposure. Ho1 inhibition by ZnPPIX decreased ZF4 cell viability under hypoxia stress, enhanced Ho1 activity protected ZF4 cell from hypoxia stress-induced cell death. These results showed that Ho1 may protect zebrafish from hypoxia-induced cell apoptosis.%实验探讨了低氧条件下血红素加氧酶1(Ho1)对斑马鱼的保护作用。Real-time PCR结果显示，低氧条件下斑马鱼ho1 mRNA水平在斑马鱼胚胎和离体培养细胞ZF4中显著增加，而在成鱼的不同组织中呈现不同的反应。低氧处理24h后，斑马鱼脑、鳃和肝脏中ho1 mRNA表达量明显上升，而在心脏和肾脏中ho1 mRNA表达量显著降低。用锌原卟啉IX(ZnPPIX)抑制ZF4细胞ho1的表达，采用CCK8试剂盒检测细胞存活率，结果显示抑制ho1表达可导致低氧条件下ZF4细胞存活率明显降低。利用Hoechst染色和caspase 3活性检测发现，在低氧条件下抑制ho1表达后ZF4细胞的凋亡率较对照组显著增加，而Ho1的诱导剂可显著降低低氧条件下抑制组的细胞凋亡率。这些结果表明斑马鱼Ho1可能通过抗细胞凋亡发挥低氧保护作用。