缺氧时肺动脉内皮细胞与肺动脉平滑肌细胞增殖的相互影响

MODULATIONS OF PROLIFERATION BETWEEN IN VITRO PULMONARY ARTERY ENDOTHELIAL CELLS AND SMOOTH MUSCLE CELLS UNDER HYPOXIA

血管内皮细胞和血管平滑肌细胞在结构和功能上关系密切，两者的相互作用参与血管舒缩和血管壁结构的调节。本文观察了培养的小牛肺动脉内皮细胞（PAECs）和肺动脉平滑肌细胞（PASMCs）缺氧时在细胞增殖方面的相互影响。PASMCs常氧条件培养基（CM）可使PAECs的3H－TdR掺入降低约58％（P＜0．01），缺氧CM对PAECs的3H－TdR掺入无明显的抑制作用；PAECs的常氧CM使PASMCs的3H－TdR掺入升高约60％，缺氧CM则明显抑制PASMCs的3H－TdR掺入（降低27％，P＜0.01）。PAECs和PASMCs混合培养24h后，常氧条件下混合细胞的相对3H-TdR降低22％（P＜0.01），2.5％O2和0％O2缺氧条件下，相对3H-TdR掺入分别升高75％和44％（P＜0.01，与常氧组相比）。与单独培养组相比，常氧或0％O2条件下共培养24h末，PASMCs的3H－TdR掺入分别升高18％和26％（P＜0．05），常氧组GI期细胞减少，G2／M期细胞增多（P＜0．01），缺氧组G1和S期细胞增多，G2／M期细胞减少（P＜0．01）；PAECs的3H-TdR掺入降低24％和38％（P＜0．01），G1和S期细胞增多，G2／M期细胞大幅度减少（P＜0.01）。上述结果表明PAECs和PASMCs在细胞增殖方面存在复杂的调节关系，其调节在缺氧时发生改变，这种改变可能参与缺氧性肺动脉高压的发生。

Vascular edothelial cells (VECs) and vascular smooth muscle cells (VSMCs) are structurally and functionally closely connected. Their interactions may play important roles in the development of hypoxic pulmonary artery hypertension. In the present study,mitogenic regulations between cultured new bovine pulmonary arterial endothelial cells (PAECs) and pulmonary arterial smooth muscle cells (PASMCs) under both normoxic and hypoxic conditions were investigated. Cell proliferation was assessed by 3H-thymidine incorporation and flow cytometry. Normoxic conditioned medium (CM) from cultured PASMCs inhibited 3H-thymidine incorporation of PAECs by 58% (P<0.01), but normoxic or hypoxic CM from PAECs promoted or inhibited 3H-thymidine incorporation of PASM by 60% and 27% respectively (P<0.01). When mixed PAECs and PASMCs were cultured for 24 h, relative 3H-thymidine incorporztion of the mixed cells decreased by 22% (P<0.01 vs monoculture) under normoxic condition,and increased by 75% or 44%under O% O2 or 2.5% O2 (P<0.01 vs normoxic mixculture). When PAECs and PASMCs were cocultured in either normoxic or hypoxic conditions, proliferation of PAECs was inhibited while that of PASMs was stimulated significantly (P<0.01), as compared with that of homotypic cultured cells. These findings suggest that PANCs and PASMCs may mutually regulate their proliferation each other, and this mutual modulation may be changed under hypoxic condition.