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, 1×10-8 and 2×10-8mol/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.%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.
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