State Key Laboratory of Medicinal Chemical Biology, The Key Laboratory of Bioactive Materials, College of Life Science, Ministry of Education, Nankai University, Tianjin 300071, China.
The Institute of Robotics and Automatic Information Systems, Nankai University, Tianjin 300071, China.
Int J Mol Sci. 2022 Jul 29;23(15):8438. doi: 10.3390/ijms23158438.
6-BA is a common plant growth regulator, but its safety has not been conclusive. The heart is one of the most important organs of living organisms, and the cardiogenesis process of zebrafish is similar to that of humans. Therefore, based on wild-type and transgenic zebrafish, we explored the development of zebrafish heart under 6-BA exposure and its mechanism. We found that 6-BA affected larval cardiogenesis, inducing defective expression of key genes for cardiac development (, , and ) and AVC differentiation (, , and ), ultimately leading to weakened cardiac function (heart rate, diastolic speed, systolic speed). Acridine orange staining showed that the degree of apoptosis in zebrafish hearts was significantly increased under 6-BA, and the expression of cell-cycle-related genes was also changed. In addition, HPA axis assays revealed abnormally expressed mRNA levels of genes and significantly increased cortisol contents, which was also consistent with the observed anxiety behavior in zebrafish at 3 dpf. Transcriptional abnormalities of pro- and anti-inflammatory factors in immune signaling pathways were also detected in qPCR experiments. Collectively, we found that 6-BA induced cardiotoxicity in zebrafish, which may be related to altered HPA axis activity and the onset of inflammatory responses under 6-BA treatment.
6-BA 是一种常见的植物生长调节剂，但它的安全性尚未得出结论。心脏是生物最重要的器官之一，斑马鱼的心脏发生过程与人相似。因此，我们基于野生型和转基因斑马鱼，探索了 6-BA 暴露下斑马鱼心脏的发育及其机制。我们发现 6-BA 影响幼鱼心脏发生，导致心脏发育关键基因（、和）和 AVC 分化（、和）的表达缺陷，最终导致心脏功能减弱（心率、舒张速度、收缩速度）。吖啶橙染色显示，6-BA 处理后斑马鱼心脏的细胞凋亡程度明显增加，细胞周期相关基因的表达也发生改变。此外，HPA 轴测定显示基因的 mRNA 水平表达异常，皮质醇含量显著增加，这与 3 dpf 时观察到的斑马鱼焦虑行为也是一致的。qPCR 实验还检测到免疫信号通路中促炎和抗炎因子的转录异常。综上所述，我们发现 6-BA 诱导斑马鱼心脏毒性，这可能与 6-BA 处理下 HPA 轴活性改变和炎症反应的发生有关。
