血小板源生长因子-AA对高血压血管平滑肌细胞钙信号的影响

EFFECT OF PDGF-AA ON [Ca^(2+)]_i IN VASCULAR SMOOTH MUSCLE CELLS IN SHRs

目的 :明确自发性高血压大鼠血管平滑肌细胞 (SHR VSMC)增殖与血小板源生长因子 AA(PDGF AA)、PDGF α受体表达的关系及钙信号在其中的作用。方法 :在培养的血管平滑肌细胞模型中 ,采用免疫印迹 (Westernblot)、3 H TdR及3 H Leu掺入、荧光探针标记测定单细胞内钙浓度等方法 ,观察不同来源大鼠 (SHR/WKY)VSMC ,PDGF AA、PDGF α受体和PDGF β受体表达的差异性以及在PDGF AA刺激下 ,VSMC增殖肥大反应、胞内 [Ca2 + ]i变化和钙离子阻断剂 (nimodipine)对其的影响。 结果 :与WKY VSMC相比SHR VSMC中PDGF AA、PDGF α受体蛋白表达明显增加 ,而PDGF β受体蛋白表达在SHR VSMC与WKY VSMC无明显变化。在PDGF AA刺激下 ,增殖细胞核抗原 (PCNA)、3 H掺入率及胞内 [Ca2 + ]i浓度在SHR VSMC明显增强 ;钙离子阻断剂 (nimodipine)明显抑制PCNA表达及3 H掺入 ,胞内 [Ca2 + ]i浓度明显下降。结论 :自发性高血压大鼠VSMCPDGF A链及其α受体的自发性增高 ,可能是导致SHR VSMC异常增殖、肥大 ,从而触发血管反应性和血管构型变化的重要原因之一 ;

Aim:To explore the relationship between proliferation and hypertrophy of vascular smooth muscle cells and PDGF AA and PDGFR αexpression in SHRs and the role of [Ca 2+ ] i in it. Methods:Express difference of PDGF AA, PDGFR α, PDGFR β in SHR/WKY VSMC was observed by Western blot. The effect of Ca 2+ inhibitor (nimodipine) on proliferation, hypertrophy and free Ca 2+ concentration of SHR VSMC induced by PDGF AA was observed by Western blot, incorporation and fluorescent digital image technique. Results: PDGF AA and PDGFR α expression was markedly increased in SHR VSMC than in WKY VSMC, but PDGFR β was not different in SHR and WKY VSMC. PDGF AA stimulated PCNA expression, incorporation and [Ca 2+ ] i increasing were observed in SHR VSMC. Dose dependent nimodipine inhibited PCNA expression, incorporation and [Ca 2+ ] i increasing induced by PDGF AA also were observed in SHR VSMC. Conclusions:Spontaneously expression increasing of PDGF AA and PDGFR α in spontaneously hypertension rats (SHRs) may be one of the important factors on vascular reactivity and vascular modeling mediated through proliferation and hypertrophy in SHR VSMC, and [Ca 2+ ] i play an important role in this process.