内皮素-1，自发性高血压大鼠平滑肌细胞的一种重要促有丝分裂原。

Endothelin-1, an important mitogen of smooth muscle cells of spontaneously hypertensive rats.

作者信息

Liu Gexiu, Wang Hua, Ou Daming, Huang Honglin, Liao Duanfang

机构信息

Institute of Pharmacy & Pharmacology of Nanhua University, Hengyang 421001, China.

出版信息

Chin Med J (Engl). 2002 May;115(5):750-2.

PMID:12133549

Abstract

OBJECTIVE

To study the features of vascular smooth muscle cell (VSMC) proliferation induced by endothelin-1 (ET-1).

METHODS

VSMCs of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats were cultured and treated with ET-1. Basic fibroblast growth factor (bFGF) gene expression was measured using both Northern blot and an enzyme-linked immunoassay.

RESULTS

ET-1 resulted in an increase in bFGF transcripts at 8 - 24 h; bFGF levels were significantly higher in VSMCs treated with ET-1 than in those not treated. However, VSMCs growth responses in SHR and WKY were different. Smooth muscle cells of SHR were hyper-responsive to ET-1. Maximal bFGF mRNA levels were elevated 3.5-fold at 4 h of stimulation in WKY and 8-fold at 8h in SHR4. Moreover, the proliferation of VSMCs induced by ET-1 was inhibited by antisense phosphorothioate oligodeoxynucleotides (10 micromol/L AS-bFGF) but not sense bFGF oligomers at the same concentrations, being reduced by 80% in SHR and 40% in WKY vs control, respectively. Furthermore, the effect of AS-bFGF oligomers on SHR SMC proliferation is significantly greater than on WKY SMC proliferation.

CONCLUSION

ET-1 may be required for exaggerated vascular growth responses in SHR and bFGF may be involved.

摘要

目的

研究内皮素-1（ET-1）诱导血管平滑肌细胞（VSMC）增殖的特征。

方法

培养自发性高血压大鼠（SHR）和Wistar-Kyoto大鼠的VSMC，并给予ET-1处理。采用Northern印迹法和酶联免疫分析法检测碱性成纤维细胞生长因子（bFGF）基因表达。

结果

ET-1导致8 - 24小时bFGF转录本增加；ET-1处理的VSMC中bFGF水平显著高于未处理的细胞。然而，SHR和WKY的VSMC生长反应不同。SHR的平滑肌细胞对ET-1反应过度。在WKY中，刺激4小时时bFGF mRNA最大水平升高3.5倍，在SHR中8小时时升高8倍。此外，ET-1诱导的VSMC增殖受到反义硫代磷酸酯寡脱氧核苷酸（10 μmol/L AS-bFGF）抑制，但相同浓度的正义bFGF寡聚物无此作用，与对照组相比，SHR中减少80%，WKY中减少40%。此外，AS-bFGF寡聚物对SHR SMC增殖的作用明显大于对WKY SMC增殖的作用。