阿利吉仑抑制血小板衍生生长因子-BB诱导的血管平滑肌增殖

Aliskiren inhibits proliferation of vascular smooth muscle cells induced by platelet-derived growth factor-BB

目的观察肾素直接抑制剂阿利吉仑对血小板衍生生长因子-BB(platelet-derived growth factor-BB,PDGF-BB)诱导的血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响及其机制。方法以大鼠胸主动脉平滑肌细胞株(A10细胞)为研究对象,观察不同浓度阿利吉仑(1、5、10μmol/L)以及PDGF-BB(20 ng/mL)对VSMCs增殖的影响,并探讨了阿利吉仑(10μmol/L)与PDGF-BB(20 ng/mL)共同刺激0、12、24、48 h时,VSMCs的增殖情况,细胞增殖采用[3H]-TdR掺入方法进行测定,ERK1/2、p-ERK1/2、β-actin蛋白表达用Western blot测定。结果 PDGF-BB可以促进A10细胞增殖,20 ng/mL PDGF-BB刺激时,细胞增殖幅度为(145.50±10.51)%,与对照组比较差异有统计学意义(P<0.05);当10μmol/L阿利吉仑与20 ng/mL PDGF-BB共同刺激时,细胞增殖幅度为(44.65±24.42)%,与20 ng/mL PDGF-BB刺激时比较有显著下降(P<0.05),而且这种抑制作用随时间的增加而增强;Western blot结果显示阿利吉仑可以降低由PDGF-BB引起的p-ERK1/2表达量的增加。结论阿利吉仑可以抑制PDGF-BB介导的促VSMCs的增殖作用,而这种作用是通过降低p-ERK1/2的磷酸化而引起的。

Objective To identify the effect of direct renin inhibitor aliskiren on the proliferation of vascular smooth muscle cells （VSMCs） induced by platelet-derived growth factor-BB （PDGF-BB）, and to study the mechanism of the effect. Methods Rat thoracic aorta smooth muscle cells （A10 cells） were used in the study. The effects of different concentrations of aliskiren （1, 5 and 10 μmol/L） and PDGF-BB （20 ng/mL） as well as 10 μmol/L aliskiren and 20 ng/mL PDGF-BB for different stimulus duration on VSMCs proliferation was observed by [3H]-TdR method. The levels of ERK, p-ERK and β-actin were assessed by immunoblotting. Results PDGF-BB could induce A10 cell proliferation, and the proliferation ratio of the cells treated with 20 ng/mL PDGF-BB was （145.50±10.51）% （P〈0.05） as compared with the control group. The proliferation ratio of the cells treated with 20 ng/mL PDGF-BB plus 10 μmol/L aliskiren was （44.65±24.42）% （P〈0.05）, which reduced as compared with that of the cells treated with 20 ng/mL PDGF-BB alone. The suppression effect of aliskiren was greater along with the stimulation duration increased. Immunoblotting results showed that the effect of aliskiren on VSMC proliferation induced by PDGF-BB might be via ERK1/2 signal pathway. Conclusion Aliskiren suppresses PDGF-BB-induced proliferation of VSMCs via ERK1/2 signal pathway.