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丹酚酸B对血小板源性生长因子-BB诱导的人主动脉平滑肌细胞增殖和迁移的作用研究
曹正旺 喻田甜 刘 坤 郑山根
联勤军事医学 ›› 2022, Vol. 36 ›› Issue (12) : 954-958.
PDF(970 KB)
PDF(970 KB)
丹酚酸B对血小板源性生长因子-BB诱导的人主动脉平滑肌细胞增殖和迁移的作用研究
目的 探讨丹酚酸B（Salvianolic acid B, Sal B）对血小板源性生长因子BB（platelet-derived growth factor-BB, PDGF-BB）诱导的人主动脉血管平滑肌细胞增殖和迁移的影响及可能机制。 方法 本研究采用20 ng/ml PDGF-BB 刺激血管平滑肌细胞建立细胞增殖模型，通过不同浓度的 Sal B (12.5，25，50和100 μmol /L)进行干预，采取 Cell Counting Kit-8实验检测细胞活性和增值，筛选 Sal B抑制血管平滑肌细胞增殖的最适浓度，通过划痕试验和Transwell 迁移实验评估Sal B对PDGF-BB诱导的血管平滑肌细胞迁移的影响。Western blot 检测增殖细胞核抗原（proliferating cell nuclear antigen, PCNA）、细胞周期蛋白D1（Cyclin D1）、周期蛋白依赖性激酶2（Cyclin-dependent kinase 2, CDK2）、基质金属蛋白酶 2（matrix metalloproteinase-2, MMP-2）、基质金属蛋白酶 9（matrix metalloproteinase-9, MMP-9）、蛋白激酶 B（protein kinase B, Akt）、细胞外信号调节激酶1/2（extracellular signal-regulated kinase 1/2, ERK1/2）表达及磷酸化水平。 结果 与对照组比较，不同剂量Sal B处理后细胞活力差异无统计学意义（P＞0.05）。与PDGF-BB组相比，50 μmol/L Sal B能显著抑制PDGF-BB刺激血管平滑肌细胞的增殖和迁移能力，显著下调细胞周期相关蛋白PCNA、Cyclin D1和CDK2蛋白表达，显著降低MMP-2、p-Akt、p-ERK1/2 的表达水平（P＜0.05），对PDGF-BB诱导的 MMP-9蛋白表达则无明显抑制作用（P＞0.05）。 结论 Sal B 可显著抑制 PDGF-BB诱导的血管平滑肌细胞增殖和迁移，其机制可能与下调 MMP-2蛋白表达及Akt、ERK1/2磷酸化水平有关。
Objective To investigate the effect and mechanism of salvianolic acid B (Sal B) on proliferation and migration of human aortic vascular smooth muscle cells (HAVSMCs) induced by platelet-derived growth factor-BB (PDGF-BB). Methods HAVSMCs were pre-incubated with different concentrations of Sal B (12.5, 25, 50, 100 μmol/L) for 1 h and then stimulated with 20 ng/ml PDGF-BB for 24 h. The cell viability and proliferation were detected by CCK-8 cell counting kit. The effects of Sal B on the migration of HAVSMCs induced by PDGF-BB were assayed in scratch test and Transwell chamber. The expressions of proliferation cell nuclear antigen (PCNA), cyclin D1, cyclin-dependent kinase 2 (CDK2), matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), p-Akt and p-ERK1/2 were detected by Western blot. Results No significant difference was found in the viability of VSMCs between control group and Sal B group. Sal B at the concentration of 50 μmol/L significantly inhibited the proliferation and migration of VSMCs stimulated by PDGF-BB, suppressed PDGF-BB induced upregulation of PCNA，Cyclin D1, CDK2 and MMP-2, but not MMP-9. Moreover, Sal B inhibited PDGF-BB-induced phosphorylation of Akt and ERK1/2. Conclusion Sal B can effectively inhibit PDGF-BB-induced VSMCs proliferation and migration, possibly via downregulating the expressions of MMP-2 and suppressing the phosphorylation of Akt and ERK1/2.
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