FIZZ1对大鼠主动脉内皮细胞血管新生的促进作用及其机制探讨  

Effects of FIZZ1 on promoting angiogenesis in rat aortic endothelial cells and its underlying mechanism

作　　者：李晓燕[1] 房洁[2] 张红明[1] 韩淑芳[1] 高玉琪[1] 晋群[1] 

机构地区：[1]济南军区总医院心内科,济南250031 [2]辽宁医学院研究生院,辽宁锦州121001

出　　处：《解放军医学杂志》2013年第2期111-115,共5页Medical Journal of Chinese People's Liberation Army

摘　　要：目的探讨抵抗素样分子α(FIZZ1)对大鼠主动脉内皮细胞血管新生的影响及其机制。方法采用贴壁法培养Wistar大鼠主动脉内皮细胞,将实验分为4组:A组(对照组)、B组(5×10–9mol/L FIZZ1组)、C组(1×10–8mol/LFIZZ1组)、D组(2×10–8mol/L FIZZ1组)。采用Matrigel小管形成实验评价不同浓度的FIZZ1对大鼠主动脉内皮细胞体外血管新生的影响。采用全基因表达谱检测FIZZ1对主动脉内皮细胞信号通路活性的影响,筛选出活性有显著差异的信号通路。结果 FIZZ1刺激后,B、C、D组新生血管数目(分别为22.6±2.9、28.5±3.3、36.9±5.0个/HP)均明显高于对照组(19.7±2.6个/HP,P<0.01),且呈剂量依赖性。全基因表达谱检测提示,FIZZ1刺激后有22条信号通路的活性出现明显改变,其中活性上调信号通路12条,如调节细胞肌动蛋白骨架通路(rno04810)等,活性下调信号通路10条,如上皮细胞细菌侵入通路(rno05100)等。结论 FIZZ1可促进大鼠主动脉内皮细胞血管新生,其机制可能与信号通路调节细胞肌动蛋白骨架通路(rno04810)活性上调有关。Objective To study the angiogenetic property of FIZZ1 on cultured rat＇s aortic endothelial cells （RAECs）, and explore its underlying mechanism. Methods The RAECs were cultured in extracellular materials （ECM） supplemented with 10% FBS. Matrigel assay was performed to assess the angiogenetic ability of RAECs after stimulation by FIZZ1 （groups A, B, C and D were control group and 5 ~ 10-9, 1 x 10-s and 2 ~ lO-Smol/L FIZZ1 group, respectively）. The Wistar rat microarray containing 41,000 genes/ESTs was used to screen the differentially expressed genes of the RAECs after stimulation by FIZZ1. Results FIZZ1 in different concentrations markedly increased the angiogenetic ability of RAECs in a dose-dependent manner （groups A, B, C and D： 19.7 _＋ 2.6, 22.6 ＋ 2.9, 28.5 ＋ 3.3 and 36.9 ＋ 5.0, respectively, P〈0.01）. By screening and analysis of the important differentially expressed genes in RAECs after stimulation by FIZZ1, 22 pathways were found to be involved, including 12 up-regulation pathways such as actin cytoskeleton pathway （rno04810）, and 10 down-regulation pathways such as bacterial invasion pathway of epithelial cells （rno05100）. Conclusion FIZZ1 may promote RAECs in angiogenesis through activation of up-regulating actin cytoskeleton pathway.

关 键 词：抵抗素样分子α 主动脉 内皮细胞 新生血管化 生理性 基因表达谱 

分 类 号：R543.5[医药卫生—心血管疾病]