【摘要】 内皮素（ＥＴ）是至今所发现的最强的内源性血管收缩肽，近年来发现ＥＴ－１能促进血管平滑肌细胞增殖。本研究表明ＥＴ－１对缺氧培养的肺动脉平滑肌细胞（ＰＡＳＭＣ）有剂量依赖的增殖作用，缺氧可促进ＰＡＳＭＣ的ＤＮＡ合成且增加ＥＴ－１的丝裂原作用。ＥＴ－１的丝裂原作用主要由其Ａ型受体（ＥＴＲ＿Ａ）所介导，ＥＴＲ＿Ａ的特异拮抗剂ＢＱ１２３可显著抑制缺氧以及缺氧与ＥＴ－１协同所产生的增殖作用，而且发现ＥＴＲ＿Ａ在缺氧培养的ＰＡＳＭＣ中的表达显著高于常氧对照组ＰＡＳＭＣ。本研究表明ＥＴ－１参与了缺氧性肺动脉结构重组，而缺氧可增强ＰＡＳＭＣ对ＥＴ－１的增殖反应性。更多还原

【Abstract】 Endothelin, a recently described vasoconstrictor,has been shown to be a mitogen forvascular smooth muscle cells. The results of the present study indicated that endothelin 1dose dependently increased the incorporation of ￣3H TdR into bovine pulmonary arterysmooth muscle cells(PASMC) cultured under hypoxic and normoxic conditions.Hypoxia stimu-lated DNA synthesis of PASMC and enhanced the mitogenic effect of ET 1 on PASMC.Themitogenic effect of ET 1 on PASMC was mediated by selective activation of ET_A receptor.BQ123,a selective ET_A receptor antagonist,not only inhibited ET 1 induced proliferation ofPASMC, but also significantly inhibited the proliferation of hypoxic and normoxic normolPASMC.The mechanism is unknown.However,it was indicated that hypoxia up-regulates thetranscription of ET_A receptor.All these suggest that endothelin might play an important role inthe proliferation of PASMC associated with hypoxic pulmonary vascular remodeling.更多还原