士的宁和氧化士的宁对斑马鱼胚胎的毒性作用。

Toxic effects of strychnine and strychnine N-oxide on zebrafish embryos.

作者信息

Li Yu, Qi Xu, Yang Yu-Wei, Pan Yang, Bian Hui-Min

机构信息

Jiangsu Key Laboratory for Chinese Medicine Processing, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210046, China; Department of Preclinical Medicine, University of Chinese Medicine, Nanjing 210046, China.

Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

出版信息

Chin J Nat Med. 2014 Oct;12(10):760-7. doi: 10.1016/S1875-5364(14)60116-3. Epub 2014 Oct 31.

DOI:10.1016/S1875-5364(14)60116-3

PMID:25443369

Abstract

AIM

The application of strychnine (S) is limited due to its toxicity; strychnine N-oxide (SNO) is a derivative of strychnine. The aim was to employ zebrafish embryos to investigate and compare the developmental toxicity induced by S and SNO.

METHODS

The toxicity of S and SNO was examined through the hatching rate and survival rate. Morphological changes of the zebrafish were observed with a dissecting microscope. Apoptosis was detected through acridine orange (AO) staining and flow cytometry. Apoptotic genes were measured by RT-PCR.

RESULTS

Embryo malformation was observed in the embryos exposed to S at 200 μmol·L(-1). When SNO concentration was increased to 1 mmol·L(-1), scoliolosis, and pericardial edema could be seen in some embryos. Results from fluorescence microscopy and flow cytometry analysis showed that S at 200 μmol·L(-1) induced apoptosis, whereas the apoptotic rate in the SNO-treated group (200 μmol·L(-1)) was much lower than that in the S group. RT-PCR analysis showed that p53 mRNA expression and the ratio of Bax/Bcl-2 in the S group were significantly altered compared with the control group (*P < 0.05). Moreover, Bax mRNA expression in both S and SNO group were significantly different from that in the control group (**P < 0.01).

CONCLUSION

These results lead to the conclusion that SNO has significantly lower toxicity than S in zebrafish embryos.

摘要

目的

士的宁（S）因其毒性而应用受限；士的宁氮氧化物（SNO）是士的宁的衍生物。本研究旨在利用斑马鱼胚胎研究并比较S和SNO诱导的发育毒性。

方法

通过孵化率和存活率检测S和SNO的毒性。用解剖显微镜观察斑马鱼的形态变化。通过吖啶橙（AO）染色和流式细胞术检测细胞凋亡。用逆转录聚合酶链反应（RT-PCR）检测凋亡基因。

结果

在暴露于200μmol·L-1 S的胚胎中观察到胚胎畸形。当SNO浓度增加到1 mmol·L-1时，在一些胚胎中可见脊柱侧凸和心包水肿。荧光显微镜和流式细胞术分析结果表明，200μmol·L-1的S诱导细胞凋亡，而SNO处理组（200μmol·L-1）的凋亡率远低于S组。RT-PCR分析表明，与对照组相比，S组p53 mRNA表达及Bax/Bcl-2比值显著改变（*P<0.05）。此外，S组和SNO组的Bax mRNA表达与对照组均有显著差异（**P<0.01）。