The Metronidazole (MTZ)/nitroreductase (NTR)-mediated cell ablation system is the most commonly used chemical-genetic cell ablation method in zebrafish. This system can specifically ablate target cells under spatial and temporal control. The MTZ/NTR system has become a widely used cell ablation system in biological, developmental, and functional studies. However, the inadequate cell-ablation ability of some cell types and the side effects of high concentration MTZ impede extensive applications of the MTZ/NTR system. In the present study, the US drug collection library was searched to extend the NTR system. Six MTZ analogs were found, and the cell-ablation ability of these analogs was tested in zebrafish larvae. The results revealed that two of the NTR substrates, Furazolidone and Ronidazole, ablated target cells more efficiently than MTZ at lower concentrations. Furthermore, the working concentration of Ronidazole, but not Furazolidone and MTZ, did not affect axonal bridge formation during spinal cord regeneration. Our results, taken together, indicate that Ronidazole is a superior prodrug to MTZ for the NTR system, especially for the study of neuron regeneration in zebrafish larvae.

甲硝唑 (MTZ)/硝基还原酶 (NTR) 介导的细胞消融系统是斑马鱼中最常用的化学遗传细胞消融方法。该系统可以在空间和时间控制下特异性地消融靶细胞。MTZ/NTR 系统已成为生物学、发育和功能研究中广泛使用的细胞消融系统。然而，某些细胞类型的细胞消融能力不足以及高浓度MTZ的副作用阻碍了MTZ/NTR系统的广泛应用。在本研究中，检索美国药物收藏库以扩展 NTR 系统。发现了六种 MTZ 类似物，并在斑马鱼幼虫中测试了这些类似物的细胞消融能力。结果表明，两种 NTR 底物，呋喃唑酮和罗硝唑在较低浓度下比 MTZ 更有效地消融靶细胞。此外，罗硝唑的工作浓度，而不是呋喃唑酮和 MTZ，不影响脊髓再生过程中轴突桥的形成。我们的结果综合起来表明，对于 NTR 系统，罗硝唑是一种优于 MTZ 的前药，特别是对于斑马鱼幼虫神经元再生的研究。