机构地区:[1]Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences University of Chinese Academy of Sciences, Shanghai 200031, China [2]Key Laboratory of Food Safety Risk Assessment, Ministry of Health, Beijing 100021, China
出 处:《Acta Pharmacologica Sinica》2013年第8期1101-1107,共7页中国药理学报(英文版)
摘 要:Aim: To investigate the embryotoxicity of dihydroartemisinin (DHA), the main active metabolite of artemisinin, in zebrafish, and explore the corresponding mechanisms. Methods: The embryos of wild type and TG (flkl:GFP) transgenic zebrafish were exposed to DHA. Developmental phenotypes of the embryos were observed. Development of blood vessels was directly observed in living embryos of TG (flkl:GFP) transgenic zebrafish under fluorescence microscope. The expression of angiogenesis marker genes vegfa, ilk1, and fit1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays. Results: Exposure to DHA (1-10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage. Furthermore, exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flkl:GFP) zebrafish line. Exposure to DHA (10 mg/L) significantly increased the mRNA expression of veEfa, flkl, and fit1 in the embryos. Knockdown of the ilk1 protein partially blocked the effects of DHA on embryogenesis. Conclusion: DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA.Aim: To investigate the embryotoxicity of dihydroartemisinin (DHA), the main active metabolite of artemisinin, in zebrafish, and explore the corresponding mechanisms. Methods: The embryos of wild type and TG (flkl:GFP) transgenic zebrafish were exposed to DHA. Developmental phenotypes of the embryos were observed. Development of blood vessels was directly observed in living embryos of TG (flkl:GFP) transgenic zebrafish under fluorescence microscope. The expression of angiogenesis marker genes vegfa, ilk1, and fit1 in the embryos was detected using real-time PCR and RNA in situ hybridization assays. Results: Exposure to DHA (1-10 mg/L) dose-dependently caused abnormal zebrafish embryonic phenotypes in the early developmental stage. Furthermore, exposure to DHA (10 mg/L) resulted in more pronounced embryonic angiogenesis in TG (flkl:GFP) zebrafish line. Exposure to DHA (10 mg/L) significantly increased the mRNA expression of veEfa, flkl, and fit1 in the embryos. Knockdown of the ilk1 protein partially blocked the effects of DHA on embryogenesis. Conclusion: DHA causes abnormal embryonic phenotypes and promotes angiogenesis in zebrafish early embryonic development, demonstrating the potential embryotoxicity of DHA.
关 键 词:ARTEMISININ DIHYDROARTEMISININ ZEBRAFISH ilk1 VEGF ANGIOGENESIS EMBRYOTOXICITY
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