摘要
目的 :证实导向药物转化生长因子α 皂草毒素蛋白Saporin (TGFα SAP)对增殖血管平滑肌细胞特异性的生长抑制作用。 方法 :用SPDP化学联结的方法合成了导向药物TGFα SAP ,并以四唑盐 (MTS)比色法和3 H 胸腺嘧啶掺入法进一步探讨了TGFα SAP对血管平滑肌细胞增殖的作用 ,及对血管平滑肌细胞和内皮细胞DNA合成的影响。 结果 :实验显示TGFα SAP对血管平滑肌细胞的增殖有明显抑制作用 ,并可使其3 H 胸腺嘧啶掺入量降低 ,而皂草毒素蛋白Saporin显示的细胞毒性作用则很弱 ;同时TGFα SAP对增殖的内皮细胞的DNA合成几乎未显示明显的细胞毒性作用。 结论 :TGFα SAP通过表皮生长因子 (EGF)受体介导较皂草毒素蛋白Saporin具有了明显增强的细胞毒性作用 ,可选择性抑制血管平滑肌细胞的增殖而对内皮细胞未显示出明显的毒性作用。
Objective:To testify the special cytotoxicity of transforming growth factor α saporin(TGFα SAP)on proliferating vascular smooth muscle cells Methods:Conjugation of saporin to TGFα was accomplished after derivation of saporin and TGFα with N succinimidy1 3 (2 pyridyldithio) proprionate Cytotoxicity effects were measured by MTS test The influence of TGFα SAP on values of thymidine incorporation into vascular smooth muscle cells and endothelium cells were measured by 3H thymidine uptake and receptor competition of TGFα SAP by adding excess TGFα to smooth muscle cells exposed to TGFα SAP Results:Biological cytotoxicity assays demonstrated that TGFα SAP significantly inhibited proliferation of smooth muscle cells in culture The absorbance measured by MTS in the treated group by TGFα SAP(10 -8 mol/L) was reduced to 50% compared with the control group However,Saporin (10 -6 10 -8 mol/L)did not significantly affect cellular proliferation The values of thymidine of TGFα SAP group (10 -9 and 10 -8 mol/L)were significantly decreased by 72% and 24% respectively compared with the control group,suggesting that cellular DNA synthesis was obviously decreased when TGFα SAP was added But adding excess TGFα to smooth muscle cells exposed to TGFα SAP inhibited the cytotoxicity of TGFα SAP 3H thymidine uptake in the group was similar compared with the blank control group But the same level of TGFα SAP did not affect endothelium cells DNA synthesis Conclusions:The results indicated that TGFα SAP possesses more effective cytotoxicity than Saporin Competition studies using excess TGFα indicated that the cytotoxic effects of SAP are specifically mediated by the EGF receptor TGFα SAP can more specifically inhibit smooth muscle cells proliferation than Saporin,but TGFα SAP does not affect endothelium cells DNA synthesis at the same level
出处
《中国循环杂志》
CSCD
北大核心
2002年第1期62-65,共4页
Chinese Circulation Journal
