摘要
目的观察血府逐瘀胶囊与血管内皮生长因子(VEGF)体外成血管作用的差异及各自对基因表达谱的影响,为中西两种药物促血管新生行为差异提供分子调控模式。方法通过血府逐瘀含药血清和VEGF影响内皮细胞HMEC-1(HMEC-1)体外成血管的结果分析,明确二者的行为差异,并确定各自最佳促血管新生的药物条件,进一步通过数字基因表达谱(DGE)技术,分析两种药物在最佳药效条件下影响基因表达的情况。结果与空白血清组比较,2.5%含药血清组作用48 h血管管腔数明显增加,5%含药血清组作用48、72 h血管管腔数明显减少(均P<0.01)。与空白组比较,1.25、2.5、5、10 ng/mL VEGF干预组血管管腔数明显增加(P<0.01)。将2.5%血府逐瘀含药血清和10 ng/mLVEGF作用48 h选定为最佳促血管新生的药物条件,进一步DGE分析的结果显示,受VEGF影响表达差异显著的基因共7个(SCGB3A1、FTPA2、IGLL5、SFTPC、SFTPA1、CD74、SFTPB),均为下调基因,共涉及百日咳、吞噬体、原发性免疫缺陷、抗原加工提呈、溶酶体、单纯疱疹感染、肺结核7条有显著差异的通路。受血府逐瘀胶囊影响的表达差异基因为5个(OTX1、BCYRN1、MRPL50、CCDC104、TCEAL1),其中OTX1表达上调,其余4个均表达下调,无差异显著的通路。结论血府逐瘀胶囊促血管生长呈现短暂及双向调控的特点,而VEGF只表现出单纯的促血管生长作用。两种药物促血管生长的行为差异与其所影响的基因密切相关。
Objective To compare the angiogenesis effect and gene expression profiles between Xuefu Zhuyu Capsule and vascular endothelial growth factor（ VEGF） in vitro on HMEC-1,to provide molecular mechanism for these two proangiogenesis medicine. Methods This study showed the different angiogenesis behavior by comparing the vessel formationin vitro between Xuefu Zhuyu-containing serum（ XZCS） and VEGF on endothelial cell HMEC-1 and picked out the respective optimum conditions for angiogenesis. Further molecular mechanism was analysed under optimum conditions by digital gene expression spectrum（ DGE）. Results Compared with the blank serum group,vessel number was increased in the 2. 5%XZCS group after induced for 48 h（P〈0. 01）,but the vessel number was decreased in the 5% XZSC group after induced for 48 and 72 h（P〈0. 01）. Compared with the control group,1. 25,2. 5,5,10 ng/mL VEGF groups were all shown to promote the vessel growth（P〈0. 01）. 2. 5% XZCS and 10 ng/m L VEGF induced 48 h were set as the optimal conditions for angiogenesis. Further DGE results showed that seven genes（ SCGB3 A1,FTPA2,IGLL5,SFTPC,SFTPA1,CD74,SFTPB）were significantly down-regulated by VEGF. Those genes were involved in seven significantly changed pathway including pertussis,phagosome,primary immunodeficiency,antigen processing and presentation,lysosome,herpes simplex infection and tuberculosis. Five genes（ OTX1,BCYRN1,MRPL50,CCDC104,TCEAL1） were remarkably changed their expression by XZCS,OTX1 expression was up-regulated and the other four were down-regulated,but showed no significantly changed pathway. Conclusions Xuefu Zhuyu Capsule could promote angiogenesis and bi-directionally control vessel growth,but VEGF showed only promotion effect on vessel growth. The different behaviors in promoting angiogenesis of those two drugs were closely related to the genes affected by the two drugs.
作者
蔡飞
王鹤
秦崇涛
胡雅琼
王一铮
高冬
宋军
CAI Fei;WANG He;QIN Chong-tao;HU Ya-qiong;WANG Yi-zheng;GAO Dong;SONG Jun(College of Integrated Traditional Chinese and Western Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou （350122.;China Academy of Chinese Medical Sci- ences Medical Experiment Center, Beijing （100700)
出处
《中国中西医结合杂志》
CAS
CSCD
北大核心
2018年第4期441-446,共6页
Chinese Journal of Integrated Traditional and Western Medicine
基金
国家自然科学基金资助项目(No.81072933
No.81173431)
关键词
血府逐瘀胶囊
血管内皮生长因子
血管新生
数字基因表达谱
Xuefu Zhuyu Capsule
vascular endothelial growth factor
angiogenesis
digital geneexpression spectrum
