CXCR4对PDGF-BB诱导的血管平滑肌细胞增殖、迁移的影响及白藜芦醇的抑制作用

The Role of CXCR4 in Proliferation and Migration of Vascular Smooth Muscle Cells and the Inhibition of Resveratrol

目的研究趋化因子受体4(Chemokine Receptor Type 4,CXCR4)对血管平滑肌细胞(Vascular Smooth Muscle Cells,VSMCs)增殖、迁移的影响及白藜芦醇(Resveratrol,RSV)的抑制作用。方法采用体外培养VSMCs,分为空白对照组、模型组[血小板源性生长因子-BB (PDGF-BB),10 ng·mL-1]、AMD3100(CXCR4特异性活性抑制剂)不同浓度给药组(1、5、10μg·mL-1)、RSV不同浓度给药组(50、100、150μmol·L-1)。采用MTT法检测细胞增殖情况;Transwell细胞穿膜实验检测VSMCs迁移能力;Western Blot法检测VSMCs的CXCR4、增殖细胞核抗原(Proliferating Cell Nuclear Antigen, PCNA)及基质金属蛋白酶2(MatrixMetalloproteinase 2,MMP2)蛋白表达情况。结果与空白对照组比较,模型组的VSMCs增殖、迁移显著增强(P<0. 01),CXCR4、PCNA及MMP2蛋白表达显著增加(P<0.05,P<0.01)。与模型组比较,AMD3100不同浓度给药组均可显著抑制PDGF-BB诱导的VSMCs增殖、迁移(P<0.05,P<0.01);RSV不同浓度给药组均可显著抑制PDGF-BB诱导的VSMCs增殖、迁移和CXCR4蛋白表达(P<0.05,P<0.01)。结论 CXCR4参与了PDGF-BB诱导的VSMCs增殖、迁移;RSV可抑制VSMCs的增殖、迁移,可能与其抑制CXCR4蛋白表达有关。

Objective To evaluate the effect of CXCR4(Chemokine Receptor Type 4)on proliferation and migration of vascular smooth muscle cells(VSMC)and the inhibitory effect of RSV(resveratrol).Methods VSMCs were cultured and divided into control group,model group(10 ng·mL-1 PDGF-BB),CXCR4 specific inhibitor AMD3100 group(1,5,10μg·mL-1)and RSV group(50,100,150μmol·L-1).Western Blot was used to detect the effect of PDGF-BB on the expression of CXCR4,PCNA(Proliferating Cell Nuclear Antigen)and MMP2(Matrix Metalloproteinase 2).MTT assay was used to detect the proliferation of VSMCs induced by PDGF-BB,and transwell test was used to detect the migration ability of VSMCs.Results Compared with the control group,PDGF-BB could significantly promote the proliferation and migration of VSMCs(P<0.01)and the expression of CXCR4,PCNA and MMP2(P<0.05,P<0.01).Compared with the model group,different concentrations of AMD3100 significantly inhibited PDGF-BB-induced cell proliferation and migration(P<0.05,P<0.01).Compared with the model group,different concentrations of RSV significantly inhibited PDGF-BB-induced cell proliferation,migration and CXCR4 protein expression(P<0.05,P<0.01).Conclusion CXCR4 is involved in the proliferation and migration of VSMCs induced by PDGF-BB.RSV can inhibit the proliferation and migration of VSMCs by inhibiting the expression of CXCR4.