血小板源生长因子-α受体结构域切除对肺血管平滑肌细胞增殖和细胞周期的影响

目的：探讨从血小板源生长因子－α（PDGF－α）受体水平阻断对肺血管平滑肌增殖的影响。方法：将组织贴块法培养的肺动脉平滑肌细胞（VSMC）分别施加小、中、大剂量的受体结构域切除的PDGF－α受体腺病毒重组体Ad5CMV-PaRtr(ACP),通过四甲基偶氮唑蓝（MTT）法观察细胞不同时相的增殖曲线；采用流式细胞学技术观察不同干预条件下VSMC细胞周期的变化。结果：中、大浓度ACP对细胞增殖有明显抑制作用。中、大剂量ACP干预后，VSMC生长明显受抑，波峰减弱或消失，第7－9天生长曲线才呈现上升趋势。在中浓度的ACP作用下，加入PDGF－BB不能促进VSMC的增殖。ACP干预前后，VSMC增殖周期中各期细胞构成发生显著的变化，以G0＋G1期细胞增多，S＋G2＋M期细胞减少为特征。与对照组相比，各组的G0＋G1期细胞均有显著升高（P＜0．05）。小剂量与中剂量、中剂量与大剂量间G0＋G1期细胞有显著性差异（P＜0．05）。结论：ACP作为细胞增殖抑制剂，能在中、大剂量下明显抑制VSMC的增殖，可使G0／G1期细胞数明显增多，且与ACP有剂量依赖关系。

Effect of Truncated PDGF-α Receptor on Cellular Cycle and Proliferation of Vascular Smooth Muscular Cells of Pulmonary Artery

OBJECTIVE: To determine the effect of truncated PDGF-alpha receptor on cellular cycle and proliferation of pulmonary artery vascular smooth muscular cells (VSMC). METHODS: Tissue mass culture was done to get vascular smooth muscular cells of pulmonary artery. Different concentrations of truncated PDGF-alpha receptor and adenoviral recombined body (Ad5CMV-PalphaRtr, ACP) were added into the cultures; the VSMC proliferation curve was observed using MTT test. The changes of VSMC cellular cycle were also observed by flow cytometry. RESULTS: ACP at mid to high concentrations can restrain the proliferation of VSMC apparently with the peak of cell growth being attenuated or eliminated. The curve presented an ascending tendency only after 7 to 9 days. Affected by mid-concentration ACP, PDGF-BB showed no significant accelerating effect on the proliferation of VSMC. The ratio of G0/G1 in cellular cycle was increased significantly in VSMC culture with ACP in comparison with control. The G0/G1 ratio also showed significant differences among different concentration ACP groups (P < 0.05). CONCLUSION: Mid-to high-concentration ACP is a powerful ihhibitor of cellular proliferation for pulmonary artery VSMC. It can increase the ratio of G0/G1 significantly and the increase seems to be ACP dosage dependent.