黄芩素抑制血管平滑肌细胞增殖作用及其机制研究

Inhibitory effect of baicalein on proliferation of vascular smooth muscle cells and its mechanism

目的探索黄芩素抑制血管平滑肌细胞(VSMC)增殖的作用以及可能机制。方法体外培养人主动脉血管平滑肌细胞(HA-VSMC),经黄芩素处理。以异硫氰酸荧光素(FITC)染色法和细胞计数试剂盒-8(CCK-8)观察HA-VSMC增殖情况,采用流式细胞术观察细胞凋亡情况。微阵列分析成纤维细胞生长因子(FGF)18基因及长链非编码核糖核酸(LncRNA)AK021954基因,实时定量聚合酶链反应(RTQ-PCR)及免疫印迹法检测FGF18 mRNA和蛋白表达量。结果黄芩素可抑制HA-VSMC的增殖并促进其凋亡。微阵列分析显示,黄芩素处理的HA-VSMC的下游靶基因中FGF 18下调最明显,而LncRNA AK021954为显著上调基因。干扰LncRNA AK021954可促进HA-VSMC的增殖并抑制凋亡。结论黄芩素可抑制VSMC的增殖并促进其凋亡,其机制可能是过表达LncRNA AK021954基因以剂量依赖方式抑制VSMC增殖,并降低FGF18的表达水平。

Objective To explore inhibitory effect of baicalein on proliferation of vascular smooth muscle cells(VSMCs)and its mechanism.Methods The human aortic vascular smooth muscle cells(HA-VSMCs) were cultured in vitro and then treated with baicalein.The HA-VSMCs proliferation through CCK-8/FITC and the apoptosis through flow cytometry were observed.The fibroblast growth factor(FGF) 18 and long noncoding RNA(LncRNA) AK021954 gene through microarray analysis were discovered.And the mRNA and protein expression of FGF 18 through RTQ-PCR and Western blot were detected.Results Baicalein can inhibit HA-VSMCs proliferation and promote its apoptosis.By analyzing microarray,of which the downstream target gene of HA-VSMCs treated with baicalein,the FGF 18 was most obvious down-regulated gene,and the LncRNA AK021954 was significantly up-regulated gene.Interfering with LncRNA AK021954 can promote HA-VSMCs proliferation and inhibit its apoptosis.Conclusion Baicalein can inhibit VSMCs proliferation and promote its apoptosis.The mechanism may be that the overexpression of LncRNA AK021954 can inhibit the proliferation of VSMCs in a dose-dependent manner and decrease the expression level of FGF18.