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前列环素类似物TFC-132对体内主动脉内膜增厚及体外平滑肌细胞增殖的抑制作用。

Inhibitory effects of prostacyclin analogue, TFC-132, on aortic neointimal thickening in vivo and smooth muscle cell proliferation in vitro.

作者信息

Asada Y, Kisanuki A, Hatakeyama K, Takahama S, Koyama T, Kurozumi S, Sumiyoshi A

机构信息

First Department of Pathology, Miyazaki Medical College, Japan.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 1994 Oct;51(4):245-8. doi: 10.1016/0952-3278(94)90187-2.

DOI:10.1016/0952-3278(94)90187-2
PMID:7846092
Abstract

Effects of a new prostacyclin analogue, TFC-132, on neointimal thickening following intimal mechanical injury and on the proliferation of cultured aortic smooth muscle cells (SMCs) were studied. The intimal injury was induced by indwelling of polyethylene tubing for 24 h in the rabbit aorta. Rabbits were killed 10 days after drawing out the tubing. TFC-132 (0.6 mg/kg or 1.2 mg/kg) was given orally at 8-h intervals through the experiment. The serum concentrations of the analogue rose significantly 1 and 2 h after administration. The mean intimal thickening in the TFC-132 treated groups was significantly thinner than in the control one. Human aortic SMCs were cultured and 3H-thymidine incorporation into DNA (DNA synthesis) was measured at the varying concentrations of TFC-132. The analogue inhibited DNA synthesis of cultured SMCs at 10(-6) and 10(-5) M. These data indicate that a new prostacyclin analogue, TFC-132, has an inhibitory effect on the neointimal thickening after intimal injury and on the aortic SMC proliferation.

摘要

研究了一种新型前列环素类似物TFC - 132对内膜机械损伤后新生内膜增厚以及对培养的主动脉平滑肌细胞(SMC)增殖的影响。通过在兔主动脉中留置聚乙烯管24小时诱导内膜损伤。拔出管子10天后处死兔子。在整个实验过程中,每隔8小时口服给予TFC - 132(0.6毫克/千克或1.2毫克/千克)。给药后1小时和2小时,类似物的血清浓度显著升高。TFC - 132治疗组的平均内膜增厚明显比对照组薄。培养人主动脉平滑肌细胞,并在不同浓度的TFC - 132下测量3H - 胸腺嘧啶核苷掺入DNA(DNA合成)的情况。该类似物在10^(-6)和10^(-5) M时抑制培养的SMC的DNA合成。这些数据表明,新型前列环素类似物TFC - 132对内膜损伤后的新生内膜增厚和主动脉SMC增殖具有抑制作用。

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2
Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-delta and by mobilization of intracellular Ca2+.血管内皮生长因子诱导的前列环素生成是由蛋白激酶C(PKC)依赖性激活细胞外信号调节蛋白激酶1和2介导的,这涉及PKC-δ以及细胞内Ca2+的动员。
Biochem J. 2001 Feb 1;353(Pt 3):503-12. doi: 10.1042/0264-6021:3530503.
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Differential regulation of extracellular signal-regulated protein kinases (ERKs) 1 and 2 by cAMP and dissociation of ERK inhibition from anti-mitogenic effects in rabbit vascular smooth muscle cells.
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Biochem J. 1999 Sep 1;342 ( Pt 2)(Pt 2):407-14.