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

作　　者：李源[1] 陈彩宇[1] 杨剑[1,2] 周发英[1] 王娜[1] 杨德忠[1] 曾春雨[1] 

机构地区：[1]第三军医大学大坪医院野战外科研究所心血管内科重庆心血管病研究所,400042 [2]第三军医大学大坪医院野战外科研究所营养科,重庆400042

出　　处：《第三军医大学学报》2013年第10期943-946,共4页Journal of Third Military Medical University

基　　金：国家重点基础研究发展计划(973计划,2012CB17801);国家自然科学基金重点项目(31130029);国家杰出青年科学基金(30925018)~~

摘　　要：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.

关 键 词：多巴胺受体 醛固酮 血管平滑肌细胞 细胞增殖 

分 类 号：R322.12[医药卫生—人体解剖和组织胚胎学] R329.8[医药卫生—基础医学]