Pro-angiogenesis effect and transcriptome profile of Shuxinyin formula in zebrafish
Pro-angiogenesis effect and transcriptome profile of Shuxinyin formula in zebrafish
复制标题
舒心饮方对斑马鱼的促血管生成作用及转录组谱。
DOI：
10.1016/j.phymed.2019.153083
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发表时间：
2019-12-01
期刊：
影响因子：
7.9
通讯作者：
Tang, Jing-Yi
中科院分区：
文献类型：
--
作者：
Zhou, Zhong-Yan;Xiao, Ying;Tang, Jing-Yi
背景：血管生成在冠心病等缺血性疾病中起着重要作用。顺心饮方是根据中医药理论开发的治疗冠心病的方剂，其作用机制尚未完全阐明。目的：本研究假设顺心饮方具有促进血管生成和微循环的作用，并探讨其作用机制。我们利用UHPLC-Q/Exactive分析系统建立了舒心饮提取物的化学特征，并在斑马鱼模型中评价了其促血管生成作用。通过斑马鱼药理实验和转录组分析相结合的方法研究了其潜在的机制。结果：SXY能显著促进斑马鱼小肠下血管丛（SIV）的生长。共处理和后处理SXY衰减VEGF受体酪氨酸激酶抑制剂II（VRI）诱导的节段间血管（ISV）的缺陷，在浓度依赖性的方式。治疗后VEGF是一种众所周知的血管生成驱动因子，也部分改善了VRI诱导的ISV缺陷。此外，SXY抑制VRI诱导的斑马鱼VEGF受体包括kdr、fltl和kdrl的下调。SXY对VRI诱导的ISV缺陷的促血管生成作用被PI 3 K和JNK抑制剂抑制，Akt抑制剂取消了SXY的促血管生成作用。结论：SXY具有促血管生成作用，其作用机制可能与VEGF/PI 3 K/Akt/MAPK信号通路、细胞连接、细胞凋亡和自噬有关。
Background: Angiogenesis plays a critical role in ischemia disease like coronary heart disease. Shunxinyin formula has been developed for treating coronary heart disease according to the principle of traditional Chinese medicine while its underlying mechanism is not fully elucidated.Purpose: Here, we hypothesize Shuxinyin formula could promote angiogenesis and microcirculation, and the underlying mechanism is also investigated.Methods: We established the chemical profile of Shuxinyin (SXY) extract utilizing a UHPLC-Q/Exactive analysis system and evaluated its pro-angiogenesis effect in zebrafish model. The underlying mechanisms were investigated by combination of pharmacological experiments with transcriptome analysis in zebrafish. Zebrafish treated with VEGF was served as the positive control in present study.Results: We found SXY significantly enhanced the sub-intestinal vessel plexus (SIVs) growth in zebrafish. Cotreatment and post-treatment SXY attenuated VEGF receptor tyrosine kinase inhibitor II (VRI)-induced deficiency of intersegmental vessels (ISVs) in a concentration dependent manner. Post-treatment VEGF, which is a well-known angiogenesis driver, also partially ameliorated VRI-induced ISVs deficiency. In addition, SXY inhibited the down-regulation of VEGF receptors, including kdr, fltl and kdrl, induced by VRI in zebrafish. The pro-angiogenesis effect of SXY on VRI-induced ISVs deficiency was suppressed by PI3K and JNK inhibitors, and Akt inhibitor abolished the pro-angiogenesis effect of SXY. The transcriptome profile of SXY preventing from VRI-induced vascular growth deficiency revealed that the underlying mechanisms were also co-related to cell junction, apoptosis and autophagy.Conclusion: We could conclude that SXY presented pro-angiogenesis effect and the action mechanisms were involved in VEGF/PI3K/Akt/MAPK signaling pathways, cell junction, apoptosis and autophagy.