【摘要】 目的 :缺氧能否通过影响血管平滑肌细胞血管活性肽的自分泌功能而参与缺氧性肺动脉高压的发生尚不明确 ,本实验在培养的新生小牛肺动脉平滑肌细胞(PASM)上探讨内皮素 1(ET 1)自分泌在其中的作用。方法 :采用3H TdR掺入研究PASM增殖 ,放免测定和斑点杂交技术研究ET 1的分泌和表达。结果 :无氧培养(0 %O2)24h使新生小牛肺动脉平滑肌细胞(PASM)的3H TdR掺入与常氧组相比增加42.3 %(P<0.001) ,ETA受体拮抗剂BQ123(10 -6mmol/L)使常氧培养的PASM的3H TdR掺入降低47 %(P<0.01) ,但对缺氧培养条件下PASM的3H TdR掺入无显著影响。采用放免测定发现 ,缺氧培养3～48h导致PASM的ET 1分泌降低非常显著(P<0.01)。斑点杂交显示 ,缺氧同样抑制PASM的ET 1的mRNA表达(P<0.01)。结论 :ET 1参与常氧情况下PASM增殖的调节 ,而与缺氧引起的PASM过度增殖无关 ,缺氧可通过抑制PASM的ET 1mRNA的表达而抑制ET 1的合成和分泌。更多还原

【Abstract】 Objective: To explore the role of alterations of autocrine function of pulmonary artery smooth muscle cells (PASMs) in the development of hypoxic pumonary hypertension (HPH). Methods: The effect of hypoxia on proliferation of cultured new born bovine PASMs and its relationship with endothelin 1 (ET 1) autocrine were investigated with 3H TdR incorporation, immunochemistry, dotting hybridization and radioimmunoassay. Results: In response to hypoxia (0%O2) for 24 h, 3H TdR inorporation of PASMs increased significantly by 42% (P<0.001 compared with control group). ETA receptor inhibitor BQ123 (10-6 mmol/L) inhibited 3H TdR incorporation by 47%(P<0.001) under normoxia, but exerted no effect under hypoxia condition. Immunochemistry showed positive staining of ET 1 in PSAM. ET 1 mRNA expression and ET 1 secretion decreased significantly when PSAMs were incubated under hypoxic condition from the 3rd to 48th h (P<0.01 vs control). Conclusion: ET 1 autocrine by PASMs regulates proloferation of themselves under nomoxia but not hypoxia. Hypoxia attenuates ET 1 synthesis and release by reducing ET 1 mRNA expression.更多还原