Effect of Danshensu derivative on angiogenesis in zebrafish / 中国药理学通报

ABSTRACT

Aim Toinvestigatethepro-angiogenic effects of Danshensu derivative ADTM and explore its underlying possible signaling pathway using zebrafish embryosasinvivomodels.Methods Theangiogenesis activities of ADTM were determined in experimental models of normal and VEGFR tyrosine kinase inhibitorⅡ(VRI )-induced vascular defective zebrafish embry-os.Embryos were treated with various concentrations (50,100,200 μmol · L-1 ) of ADTM for indicated time.The diameter and the numbers of endothelial cells of zebrafish SIVs were evaluated,respectively.In VRI model,the number of intact and defective ISVs in each zebrafish embryo was counted.The total RNA of zebrafish embryos was extracted and transcriptional profiling was analyzed by deep sequencing.Quantita-tive real-time PCR(qPCR)was performed to 4 genes selected from transcriptional profiling to validate the data collected from transcriptome analysis.Results ADTMsignificantlyincreasedsubintestinalvessels (SIVs)diameter in a concentration-dependent manner in normal zebrafish as well as restored VRI-induced blood vessels defect in VRI-exposed zebrafish. The transcriptome data analysis demonstrated that 19 signif-icantly changed genes were mapped to insulin signaling pathway.The qPCR data are in good agreement with those obtained by deep sequencing and support the consistency between the two methods for determining relative expression levels in the zebrafish model.Con-clusion Inzebrafishmodel,ADTMexhibitsthe effects of angiogenesis and blood vessel restoration. The underlying mechanism may be involved in the acti-vation of insulin signaling pathway.