[1]杨玉莹,李平灯,金英伟,等.全反式维甲酸暴露对斑马鱼的神经毒性效应[J].武汉工程大学学报,2021,43(04):376-380.[doi:10.19843/j.cnki.CN42-1779/TQ. 202104012]
YANG Yuying,LI Pingdeng,JIN Yingwei,et al.Effect of All-Trans-Retinoic Acid Exposure on Neurotoxicity of Zebrafish[J].Journal of Wuhan Institute of Technology,2021,43(04):376-380.[doi:10.19843/j.cnki.CN42-1779/TQ. 202104012]
点击复制
全反式维甲酸暴露对斑马鱼的神经毒性效应(/HTML)
《武汉工程大学学报》[ISSN:1674-2869/CN:42-1779/TQ]
- 卷:
-
43
- 期数:
-
2021年04期
- 页码:
-
376-380
- 栏目:
-
化学与化学工程
- 出版日期:
-
2021-08-31
文章信息/Info
- Title:
-
Effect of All-Trans-Retinoic Acid Exposure on Neurotoxicity of Zebrafish
- 文章编号:
-
1674 - 2869(2021)04 - 0376 - 05
- 作者:
-
杨玉莹1; 李平灯1; 金英伟1; 丁 强1; 户业丽*2
-
1. 武汉工程大学环境生态与生物工程学院,湖北 武汉 430205;2. 宜昌三峡制药有限公司,湖北 宜昌 443004
- Author(s):
-
YANG Yuying1; LI Pingdeng1; JIN Yingwei1; DING Qiang1; HU Yeli*2
-
1. School of Environmental Ecology and Bioengineering,Wuhan Institute of Technology,Wuhan 430205,China;2. Yichang Sanxia Pharmaceutical Co., Ltd, Yichang 443004,China
-
- 关键词:
-
全反式维甲酸; 斑马鱼; 神经毒性
- Keywords:
-
all-trans retinoic acid; zebrafish; neurotoxicity
- 分类号:
-
G633.91
- DOI:
-
10.19843/j.cnki.CN42-1779/TQ. 202104012
- 文献标志码:
-
A
- 摘要:
-
探讨全反式维甲酸(atRA)暴露对斑马鱼胚胎及幼鱼神经毒性效应和机制。以不同浓度(0,5,10和20 nmol/L)的atRA暴露斑马鱼胚胎,并探讨了斑马鱼自发胎动、幼鱼运动活力、可视化mbp荧光蛋白及神经相关基因表达与atRA暴露的关系。研究结果显示,与对照组相比,10和20 nmol/L的atRA暴露可显著降低斑马鱼胚胎自发运动活力,分别下降25.6%和50.8%;atRA处理下,幼鱼对光暗转换的刺激较为敏感,幼鱼总运动距离和运动速度均出现显著下降;20 nmol/L atRA暴露使得斑马鱼大脑中mbp蛋白表达减少38.7%,大脑形态的缺陷以及脑部神经复杂程度也相应减少。此外,髓磷脂碱性蛋白mbp以及突触素蛋白syn2a mRNA表达量仅为对照组的41.2%和54.6%。以上研究结果显示:atRA对斑马鱼胚胎及幼鱼具有显著的神经毒性,并且可以通过抑制mbp与syn2a的表达干扰斑马鱼胚胎早期的神经发育及行为活力。
- Abstract:
-
The neurotoxic effects and mechanism of all-trans-retinoic acid (atRA) in embryo and larval zebrafish were investigated in the present work. Embryo and larval zebrafish were exposed to different concentrations of atRA(0, 5, 10 and 20 nmol/L) to explore the effects of atRA on the embryonic spontaneous movement, larval swimming speed, visual mbp (myelin basic protein) fluorescent protein and neuro-related gene expression in zebrafish. The results showed that, compared with the control group, the spontaneous motor activity of zebrafish embryos is significantly reduced by 25.6% and 50.8% after the exposure to 10 and 20 nmol/L atRA, respectively. Meanwhile, the larval fish are more sensitive to the stimulation of light to dark switching, and the total movement distance and average movement speed of larval fish decrease significantly with atRA treatment. Furthermore, the exposure to 20 nmol/L atRA results in a decreased expression of mbp protein by 38.7% in the brain of zebrafish, defective brain morphology and decreased neurocomplexity.In addition, the mRNA expression levels of myelin basic protein mbp and synaptophysin protein syn2a are only 41.2% and 54.6% of those in the control group. These results suggest that atRA has significant neurotoxicity on zebrafish embryos and larval fish, which can interfere with the early neurodevelopment and behavioral activity of zebrafish embryos by inhibiting the expression of mbp and syn2a.
参考文献/References:
[1] 蒋鹏. 全反式维甲酸一般药理学、急性毒性和长期毒性研究[D].杭州:浙江大学,2016.[2] NAVARRO-MARTIN L, OLIVEIRA E, CASADO M, et al. Dysregulatory effects of retinoic acid isomers in late zebrafish embryos[J]. Environmental Science and Pollution Research, 2018,25(4):3849-3859.[3] DELPHINE G, BOUYER C, NGUYEN E, et al. Complex context relationships between DNA methylation and accessibility, histone marks, and hTERT gene expression in acute promyelocytic leukemia cells: perspectives for all‐ trans retinoic acid in cancer therapy[J]. Molecular Oncology, 2020, 14(6): 1310-1326.[4] WANG W J, ZONG G, WANG L, et al. All-trans retinoic acid exerts selective anti-FLT3-ITD acute myeloid leukemia efficacy through downregulating Chk1 kinase[J]. Cancer Letters, 2020, 473 :130-138.[5] SZYMANSKI L, SKOPEK R, PALUSINSKA M, et al. Retinoic acid and its derivatives in skin[J]. Cells, 2020, 9(12) : 2660-2660.[6] 叶瑞贤,梁晓冬,邓婕,等.口服维甲酸在治疗皮肤病的应用[J].中国中西医结合皮肤性病学杂志,2020,19(5):497-500.[7] 陈雁虹,盖仁华,吴洪海.全反式维A酸给药4周对大鼠的毒性作用[J].中国药理学与毒理学杂志,2013,27(2):248-255.[8] 路璐,李盛林,俞光岩,等.利用人胚胎干细胞评价反式维甲酸的胚胎发育毒性[J].科学技术与工程,2014,14(24):23-27.[9] 夏晓雪,缪旭,张冬梅,等.维甲酸类药物的临床应用及对生殖的影响[J].皮肤病与性病,2020,42(4):498-501.[10] BORRACCI P, CARRATU M R. Rat embryo exposure to all-trans retinoic acid results in long-term cognitive deficits[J]. European Review for Medical and Pharmacological Sciences,2014,18(1):28-33.[11] COLUCCIA A, BORRACCI P, BELFIORE D, et al. Late embryonic exposure to all-trans retinoic acid induces a pattern of motor deficits unrelated to the developmental stage[J]. Neurotoxicology,2009,30(6):1120-1126.[12] FITZGERALD J A, KONEMANN S, KRUMPELM-ANN L, et al. Approaches to test the neurotoxicity of environmental contaminants in the zebrafish model: from behavior to molecular mechanisms[J]. Environmental Toxicology and Chemistry, 2021,40(4):989-1006.[13] 郭弘扬,唐天乐,朱晓鹏.斑马鱼模型在中枢神经系统疾病中的研究进展[J].中国海洋药物,2020,39(3):71-79.[14] 李佳妮,陈将飞,董昊嘉,等.LM609联合TBBPA对斑马鱼神经行为毒性的影响[J].浙江农业科学,2021,62(4):795-799,805.[15] TORVUND-JENSEN J, STEENGAARD J, ASK-EBJERG L B, et al. The 3 ’ UTRs of myelin basic protein mRNAs regulate transport, local translation and sensitivity to neuronal activity in zebrafish[J]. Frontiers in Molecular Neuroscience,2018,11:185:1-14.[16] 李红燕,谢倩,王成,等.斑马鱼在药物毒理学评估中应用及机制的研究进展[J].中草药,2021,52(1):278-288.[17] SHI Q P, WANG M, SHI F Q, et al. Developmental neurotoxicity of triphenyl phosphate in zebrafish larvae [J]. Aquatic Toxicology, 2018,203:80-87.
备注/Memo
- 备注/Memo:
-
收稿日期:2021-04-09作者简介:杨玉莹,硕士研究生。E-mail: [email protected]*通讯作者:户业丽,硕士,教授,硕士生导师。E-mail: [email protected]引文格式:杨玉莹,李平灯,金英伟,等. 全反式维甲酸暴露对斑马鱼的神经毒性效应[J]. 武汉工程大学学报,2021,43(4):376-380.
更新日期/Last Update:
2021-08-07