多巴胺D3受体对醛固酮介导的血管平滑肌细胞增殖的影响

D_3 dopamine receptor suppresses aldosterone-induced proliferation of vascular smooth muscle cells

目的观察多巴胺D3受体对醛固酮介导的血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响。方法以大鼠胸主动脉平滑肌细胞株(A10细胞)为研究对象,观察在醛固酮10-10～10-7mol/L、多巴胺D3受体激动剂(PD128907)10-10～10-7mol/L分别单独作用,醛固酮10-7mol/L、PD128907 10-10～10-7mol/L共同作用以及D3受体拮抗剂(U99194A)、PD128907 10-7mol/L和醛固酮10-7mol/L共同作用的情况下,A10细胞增殖幅度的变化,细胞增殖用3H-胸腺嘧啶核苷掺入法测定。Western blot检测ERK1/2、p-ERK1/2表达。结果醛固酮呈浓度依赖性地促进A10细胞的增殖,其最大促增殖作用幅度达(65±6)%(P<0.05)。PD128907本身对A10细胞增殖无影响,但PD128907可通过D3多巴胺受体减弱醛固酮(10-7mol/L)介导的A10细胞增殖,在10-7mol/L浓度时可使促增殖幅度降低至(12±6)%(P<0.05),应用D3受体阻断剂U99194A后该抑制作用丧失。PD128907能够降低醛固酮(10-7mol/L)对ERK1/2信号的磷酸化激活效果。结论多巴胺D3受体激活对醛固酮介导的促VSMCs增殖有明显抑制效应。

Objective To investigate the effect of D3 dopamine receptor on aldosterone-induced proliferation of vascular smooth muscle cells （VSMCs）. Methods A10 cells （rat aortic vascular smooth muscle cells） were incubated with different concentrations of aldosterone from 10-10 to 10-7 mol/L in presence or absence of D3 dopamine receptor agonist PD128907 （10-10 to 10-7） and antagonist U99194A. The proliferation of VSMCs was determined by [3H]-TdR incorporation. The expression of ERK1/2, p-ERK1/2 were detected by Western blotting. Results Aldosterone treatment resulted in an increased proliferation of VSMCs in a dose-dependent manner with a maximal proliferative amplitude of （65±6）% （P〈0.05）. Although D3 dopamine receptor agonists PD128907 had no effect on the proliferation of VSMCs by itself, it effectively blocked the aldosterone-mediated proliferation of VSMCs and lowered the proliferative amplitude to （12±6）% （P〈0.05）, probably through ERK1/2 pathway. Conclusion Activation of D3 receptor inhibits aldosterone-mediated proliferation of VSMCs.