NPY-Y1受体激动剂对SHR脑血管平滑肌细胞的促增殖作用

Proliferation Effect of Neuropeptide Y-Y1 Receptor Agonist on Cerebrovascular Smooth Muscle Cells

目的探讨NPY-Y1受体激动剂[Leu31,Pro34]-NPY对体外培养的自发性高血压大鼠(SHR)脑血管平滑肌细胞增殖周期的影响及其跨膜信号传递途径。方法植块法培养SHR血管平滑肌细胞,流式细胞仪检测不同药物干预下S期细胞的百分比;激光共聚焦扫描显微镜定量分析细胞内游离钙离子浓度。结果随着[Leu31,Pro34]-NPY浓度的增加,S期细胞所占百分比增加,10-5、10-6mol/L NPY组与对照组相比有显著差异(P<0.05)。[Leu31,Pro34]-NPY(用正常细胞外液稀释)干预细胞时,细胞内游离钙离子浓度先明显升高,随后下降(P<0.01);[Leu31,Pro34]-NPY+硝苯地平组细胞内钙离子浓度变化不明显,而硝苯地平组细胞内钙离子浓度呈下降趋势(P<0.01)。结论通过细胞膜上L型钙离子通道进行跨膜信号传递,NPY-Y1受体介导促血管平滑肌细胞增殖作用。

Objective To investigate the pathway and mechanism of neuropeptide Y（NPY）-Y1 receptor agonist, [ Leu^31 , Pro^34 ] -NPY, on the cultured cerebrovascular smooth muscle cells （SMCs） in the spontaneously hypertensive rats（SHR） in vitro. Methods The SMCs of the arteries from the brain of SHR were cultured in vitro. Cell cycle was detected with flow cytometry, and the concentration of free intracellular calcium was examined with laser scanning confocal microscopy. Results The percentages of S stage cells of 10^-5 mol/L and 10^-6 mol/L NPY was higher than those of the control group （P 〈 0.05）. [ Leu^31 , Pro^34 ]-NPY could increase the concentration of intracellular free calcium, but the concentration decreased later （P 〈 0.01 ）. [ Leu^31 , Pro^34 ] -NPY ＋ nifedipine could not affect the concentration of calcium,while nifedipine could decrease the concentration of intracellular calcium （P 〈0.01 ）. Conclusion Through the signal pathway of L-type calcium channel on the cytomembrane, NPY-Y1 receptor could increase the proliferation of SMCs.