表皮生长因子对离体大鼠肺动脉及肺动脉平滑肌细胞作用的研究

STUDIES ON EFFECT OF EPIDERMAL GEROWTH FACTOR ON RAT PULMONARY ARTERY IN VITRO AND CULTURED PULMONARY ARTERIAL SMOOTH MUSCLE CELLS

本研究着重探讨表皮生长因子（ＥＧＦ）对大鼠肺动脉的收缩作用及对肺动脉平滑肌细胞分裂增殖的影响。浓度为１×１０－９－１×１０－７ｍｏｌ／Ｌ的ＥＧＦ可引起大鼠肺动脉剂量依赖性收缩（ｒ＝０．９６８，Ｐ＜０，００１），其Ｅｍａｘ为１００．６ｍｇ，ＥＣ５０为１１．９６ｎｍｏｌ／Ｌ。在同时存在０．５％胎牛血清（ＦＣＳ）时，ＥＧＦ能促进平滑肌细胞的３Ｈ－ＴｄＲ参入率，该作用与剂量呈正相关（ｒ＝０．８２３，Ｐ＜０．０５），其ＥＣ５０为６．５×１Ｏ－１２ｍｏｌ／Ｌ。１×１０－９ｍｏｌ／Ｌ的ＥＧＦ＋０．５％ＦＣＳ能产生与１０％ＦＣＳ相当的促细胞分裂增殖能力（在培养的第１，３，５，７天，二者促分裂增殖能力相差不明显，Ｐ均＞０．０５，第９天时，前者大于后者，Ｐ＜０．０５）。１×１０－９ｍｏｌ／ＬＥＧＦ单独存在时对平滑肌细胞未显示出明显的致分裂活性。上述作用提示ＥＣＦ在某些肺血管病变如缺氧性肺动脉高压中可能有一定意义。

The effects of epidermal growth factor(EGF) on contraction of rat pulmonary artery andproliferation of cultured pulmonary arterial smooth muscle cells were observed. The resultsshowed that EGF at concentrations ranged from 1×10-9 to 1×10-7mol/L caused dose-de-pendent(r=0.968, P<0.001) contraction of vessel rings of rat intrapulmonary artery withEmax of 100.6 mg and EC50 of 11.96nmol/L. When rat pulmonary arterial smooth muscle cellswere cultured in the presence of 0.5% fetal calf serum(FCS), EGF at concentrations ranged from1×1O-12 to 1×10-9mol/L also stimulated 3H-thymidine incorporation in confluent quiescentmonolayers in a dose-dependent manner(r=0.823,P<0.05), with EC50 being 6.5× 10-12mol/L. The presence of FCS at low concentration(0.5%) was required for EGF to elicit aproliferative response and 1×10-9mol/L EGF+0.5%FCS stimulated growth of these culturedcells to the same extent as that ellcited by 10%FCS. These results demonstrate that EGF is both avasconstrictor and a mitogen for rat pulmonary arterial smooth muscle cells, and may play a rolein hypoxic pulmonary hypertension.