血小板源生长因子可促进低氧的牛肺动脉平滑肌细胞核内NF-κB表达

Platelet-derived growth factor stimulate the increase of NF-κB expression in the nuclei of hypoxic bovine pulmonary artery smooth muscle cells

目的：为探讨血小板源生长因子（ｐｌａｔｅｌｅｔ－ｄｅｒｉｖｅｄ ｇｒｏｗｔｈ ｆａｃｔｏｒ，ＰＤＧＦ）受体信号转导途径的介质分子之一过氧化氢（Ｈ２Ｏ２）在低氧的肺动脉平滑肌细胞（ｐｕｌｍｏｎａｒｙ ａｒｔｅｒｙ ｓｍｏｏｔｈ ｍｕｓｃｌｅ ｃｅｌｌ， ＰＡＳＭＣ）增殖中是否起作用。方法：应用共聚焦显微镜、细胞免疫组织化学及Ｗｅｓｔｅｒｎ印迹杂交等方法，检测了低氧的 ＰＡＳＭＣ ＰＤＧＦ受体途径中的Ｈ２Ｏ２的变化及ＰＤＧＦ和Ｈ２Ｏ２对细胞核内与增殖作用相关的核转录日子ＮＦ－κＢ表达量的影响。结果：ＰＤＧＦ可使常氧的 ＰＡＳＭＣ中 Ｈ２Ｏ２浓度增高，但明显降低低氧的 ＰＡＳＭＣ中 Ｈ２Ｏ２的量；同一浓度的 Ｈ２Ｏ２，作用于常氧的ＰＡＳＭＣ，则引起核ＮＦ－κＢ的表达量增加，但对低氧的ＰＡＳＭＣ核ＮＦ－κＢ有明显的抑制作用；同时加入ＰＤＧＦ和Ｈ２Ｏ２的低氧的ＰＡＳＭＣ较仅以Ｈ２Ｏ２作用的低氧的ＰＡＳＭＣ，核ＮＦ－κＢ的量显著增加。结论：ＰＤＧＦ受体的信号转导途径在低氧的ＰＡＳＭＣ同常氧的ＰＡＳＭＣ相反，Ｈ２Ｏ２为抑制因子，对细胞可能产生损伤作用，ＰＤＧＦ可抑制低氧的ＰＡＳＭＣ产生Ｈ２Ｏ２并达到促进ＮＦ－κＢ表达增强的目的，

AIM: To reveal whether H2O2, a kind of platelet - derived growth factor (PDGF) signaling molecule, involved in the proliferation of phypoxic pulmonary arlmonary artery smooth muscle cells (PASMCs) and expression of transcription factor NF -κB. METHODS: bar confocal scanning microscopy,immunocytochemistry and Western blot analysis were used. RESULTS: PDGF (30 ng/mL) elevated the intracellular H2O2 in normoxic PASMCs, but decreased that of hypoxic PASMCs significantly. When 100μmol/L H2O2 was added, NF - κB expression were inhib- ited markedly in hypokic PASMCs, while the same concentration H2O2 resulted in increase of NF - κB expression in control cells. CONCLUSION: H2O2, a mediator molecule of PDGF signal transduction, act as an inhibitor in hy- poxic PASMCs which is qUiet different from that in normoxic PASMCs. It may effect on the expression of transcription factor NF -κB. NF - κB induce various gene expression that involving in the proliferation of vascular smooth muscle cells. One mechanism by which PDGF - induced hypoxic PASMC proliferation might be through PDGF alleviating H2O2 inhibition.