TP40对血管平滑肌细胞增殖的抑制作用
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Inhibitory effect of TP40 on vascular smooth muscle cell proliferation
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    摘要:

    目的:探讨转化生长因子α(TGFα)-绿脓杆菌外毒素(PE40)融合蛋白(TP40)对血管平滑肌细胞(SMC)增殖的抑制作用。方法:用免疫组化ABC法检测原代培养增殖期及静止期SMC表皮生长因子受体(EGFR)的表达,用结晶紫染色法和3H-亮氨酸掺入法检测TP40对增殖期和静止期SMC增殖及蛋白质合成的抑制,用过量EGF竞争抑制TP40的细胞毒作用。结果:增殖期SMC能高水平表达EGFR,静止期SMC表达水平较低。TP40浓度为0.1和1.0 ng/ml时,对增殖期SMC增殖及蛋白质合成的抑制作用与静止期SMC无差异(P>0.05);10及100 ng/ml时,对增殖期SMC增殖及蛋白质合成的抑制作用较静止期SMC强(P<0.01);过量EGF能完全抑制TP40的细胞毒作用。结论:TP40对增殖期SMC的增殖具有较强的抑制作用,对静止期SMC则影响较小,作用部位为细胞的EGFR。

    Abstract:

    Objective: To investigate inhibitory effect of recombinant TGFα-PE40 (TP40) on cultured vascular smooth muscle cells (SMC). Methods: Expression of epidermal growth factor receptor (EGFR) in SMC was analysed with immunohistochemistry. Inhibitory effects of TP40 on SMC proliferation and protein synthesis were analysed by crystal violet staining and 3H-leucine incorporation. Competition assays were performed by the addition of excess of EGF. Results: Expression of EGFR was found in rapidly proliferating SMC, not found in quiescent SMC. Inhibitory effects of TP40 on rapidly proliferating SMC proliferation and protein synthsis was much higher than on quiescent SMC. Excess EGF can completely block inhibitory effects of TP40. Conclusion: It indicates that TP40 can significantly inhibit the proliferation of rapidly proliferating SMC, but less confluence quiescent SMC. The cytotoxic effects of TP40 are specifically mediaed by EGFR.

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