1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐对内皮素促血管平滑肌细胞增殖及癌基因表达的影响

采用内皮素-1(ET-1 0.1 μmol·L^-1)建立培养的血管平滑肌细胞增殖模型，用［³H］胸腺嘧啶核苷(［³H］TdR)参入法, 流式细胞术, 免疫细胞化学及Northern blot方法, 观察了1-(2,6-二甲基苯氧基)-2-(3,4-二甲氧基苯乙氨基)丙烷盐酸盐(DDPH 0.1 μmol·L^-1)对血管平滑肌细胞增殖的作用及对原癌基因及抑癌基因的影响. 结果发现: DDPH能逆转ET-1所致［³H］TdR参入量增多, 阻止血管平滑肌细胞由静止期 (G₀/G₁期)进入DNA合成期(S期)和有丝分裂期(G₂/M期), 并能逆转ET-1引起的c-fos, c-myc, c-sis原癌基因相关抗原及 mRNA表达增强, P53抑癌基因相关抗原及mRNA表达减弱. 提示DDPH能抑制血管平滑肌细胞增殖, 与癌基因调控的分子生物学机理有关.

Effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxyphenyl-ethylamino) propane hydrochloride on endothelin-stimulated proliferation of vascular smooth muscle cells and expression of oncogenes

In order to determine the effects of 1-(2,6-dimethylphenoxy)-2-(3,4-dimethoxy-phenylethylamino) propane hydrochloride (DDPH 0.1 μmol·L^-1) on endothelin- 1 (ET-1 0.1 μmol·L^-1) stimulated proliferation of vascular smooth muscle cells (VSMC) and expression of oncogene c-myc, c-fos, c-sis, and antioncogene P53, the experimental models of proliferation of cultured porcine aortic smooth muscle cells induced by ET-1 were established, and ［³H］thymidine (［³H］TdR) incorporation, flow cytometry, immunohistochemistry and Northern blot assays were used. The results showed that DDPH may drop ［³H］TdR data increased by ET-1 and hold-back VSMC from static phase (G₀/G₁) to DNA synthetic phase (S) and mitotic phase (G₂/M). Furthermore, DDPH could reverse the enhanced expression of oncogene c-myc, c-fos, c-sis and reduced expression of antioncogene P53 induced by ET- 1. These results suggest that DDPH may inhibit DNA synthesis and proliferation of VSMC, related with the mechanism of molecular biology of controlling oncogene.