肝素及小肝素分子对培养平滑肌细胞的双重调节作用

Dual Effect of Heparin and Low Molecular Weight Heparin on Cultured Smooth Muscle Cells

为研究肝素及小肝素分子对培养的平滑肌细胞生长的作用 ,以探讨其是否可以作为一种抗血管平滑肌细胞增殖的药物 ,采用3H -胸腺嘧啶脱氧核苷掺入法观察肝素及小肝素分子对培养的人主动脉平滑肌细胞合成DNA的影响。肝素及小肝素分子的量以糖醛酸表示 ,以其浓度计算 (18、35和 70mg/L)。结果发现 ,肝素及小肝素分子对生长良好的平滑肌细胞有抑制作用 ,不同浓度肝素的抑制率分别为 6 6 %、6 9%和 6 9% ,而不同浓度小肝素分子抑制率分别为 6 0 %、6 8%和 6 7%。肝素及小肝素分子对生长不良的平滑肌细胞有促增殖作用 ,肝素促增殖率为149%、140 %和 180 % ,小肝素分子为 2 0 7%、2 46 %和 30 9%。结果提示肝素及小肝素分子对培养不同状态的平滑肌细胞有抑制或促进增殖的双重调节作用。

Aim The effects of heparin and low molecular weight heparin (LMWH) on the growth of cultured human aortic smooth muscle cells(hASMCs) was studied in this article. Methods The thirth-passage hASMCs were planted onto 24-well plate. After incubated for 24 h in media supplemented with 10%human serum(HS) and 10%fetal calf serum(FCS), media were changed into low concentration serum(0.5% HS, 0.5%FCS)and continued to incubate for 24 h and cultured by DMEM containing 10%HS either old or fresh, 10%FCS and different concentration of heparin or LMWH (heparin and LMWH were presented as hexuronic acid) together with corresponding control groups (without heparin or LMWH) for 24 h, hASMCs growth was estimated both morphologically and by 3 H-TdR incorporation. Results Both heparin and LMWH inhibited the proliferation of well-growth hASMCs, the inhibition rates were 66%, 69%, 69%, and 60%, 68%, 67%, respectively, with no concentration dependent relationship. hASMCs of control (with old HS stored at 4℃ for 2 years) shrank and showed poor-growth pattern while those in groups of different concentrations of LMWH or heparin became well-spread and well-growth pattern. Both heparin and LMWH promoted the proliferation of poor-growth hASMCs, the stimulation rates were 149%, 140%, 180%, and 207%, 246%, 309%, respectively. Conclusions Heparin and LMWH have a dual regulative role (inhibition and promotion) in hASMCs growth. It indicate that they may play an important role in controlling the proliferation of vascular smooth muscle cells and maintaining the integrity of vascular structure.