多巴胺D_1类受体对神经肽Y受体介导的促血管平滑肌细胞增殖的影响

D_1-like dopamine receptor suppresses neuropeptide Y-induced proliferation in vascular smooth muscle cells

目的探讨多巴胺D1类受体对神经肽Y(neuropeptide Y,NPY)受体介导的Sprague-Dawley(SD)大鼠原代血管平滑肌细胞(vascular smooth muscle cells,VSMCs)增殖的影响。方法以NPY(10-8～10-11mol/L)刺激SD大鼠胸主动脉培养的VSMCs,观察在D1类多巴胺受体激动剂Fenoldopam(10-8mol/L)存在的情况下,神经肽Y促VSMCs增殖作用的变化。细胞增殖的检测采用[3H]胸腺嘧啶核苷([3H]-TdR)掺入率的变化表示及MTT方法。结果 NPY呈浓度依赖性促进SD大鼠VSMCs的异常增殖,最高增殖幅度达(77±9)%(P<0.05),该增殖作用由NPY Y1受体亚型介导。多巴胺D1类受体激动剂Fenoldopam对VSMCs无增殖影响,但Fenoldopam可抑制NPY Y1亚型受体介导VSMCs的增殖作用,该作用通过PKA途径发挥作用。结论多巴胺D1类受体激活抑制NPY受体介导的促VSMCs增殖作用,可能参与心血管疾病的发生、发展过程。

Objective To determine the effect of D1-like dopamine receptor on neuropeptide Y（NPY）-mediated proliferation in primary cultured vascular smooth muscle cells（VSMCs） derived from thoracic aorta of Sprague-Dawley（SD） rats.Methods After VSMCs were isolated from SD rat thoracic aorta and identified by morphology and immunocytocchemistry,the cells at passage 4 to 8 were treated by 10-8 to 10-11 mol/L NPY in presence or absence of D1-like receptor agonist fenoldopam（10-8 mol/L）,blocker BIBP3226（10-6 mol/L）,or antagonist SCH23390（10-8 mol/L）to observe NPY-mediated proliferation in VSMCs.The proliferation of VSMCs was investigated by -TdR incorporation and MTT assay.Results NPY resulted in an increased proliferation of VSMCs in a concentration-dependent manner,with a maximal proliferative amplitude of（77±9）%（P0.05）.D1-like receptor agonist,fenoldopam,completely blocked the NPY Y1-mediated proliferation in VSMCs,although the agonist had no effect on the proliferation of VSMCs by itself,which might be through protein kinase A pathway.Conclusion Activation of D1-like receptor inhibits NPY Y1-mediated proliferation in VSMCs,which might be involved in the pathogenesis of cardiovascular diseases.