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

内皮素-1是自发性高血压大鼠平滑肌细胞的有丝分裂剂(英文)

作　　者：刘革修[1] 王华[1] 欧大明[1] 黄红林[1] 廖端芳[1] 

机构地区：[1]南华大学药物药理研究所,衡阳421001

出　　处：《Chinese Medical Journal》2002年第5期750-752,156,共3页中华医学杂志（英文版）

基　　金：ThisprojectwassupportedbytheNationalMajorBasicProgram(G2 0 0 0 5 690 5 ) ;NationalNaturalScienceFoundationofChina(3 9470 80 9)

摘　　要：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.目的　研究自发性高血压大鼠平滑肌细胞增殖特性。方法　采用细胞培养、核酸杂交、酶联免疫法及反义核酸技术检测内皮素对自发性高血压大鼠和Wistar kyoto大鼠的血管平滑肌细胞增殖、碱性成纤维细胞生长因子表达的影响 ,并进行对比分析。结果　内皮素 1诱导了血管平滑肌细胞的增殖 ,且诱导了其碱性成纤维细胞生长因子的表达。但是内皮素 1对自发性高血压大鼠血管平滑肌细胞增殖作用显著高于对Wistar kyoto大鼠血管平滑肌细胞 ,对它们碱性成纤维细胞生长因子表达作用也不相同 ,作用峰值分别为 8倍和 3 5倍 ,且到达峰值时间不同 ,分别为 8h和 4h。且反义核酸对内皮素 1诱导的自发性高血压大鼠血管平滑肌细胞增殖的抑制作用 (80 % )显著强于对内皮素 1诱导的Wistar kyoto大鼠血管平滑肌细胞增殖的抑制作用 (40 % ) (P <0 0 1)。结论　内皮素 1在自发性高血压大鼠平滑肌细胞增殖中具有重要作用 ,碱性成纤维细胞生长因子可能介导该作用。

关 键 词：Animals Cell Division Cells  Cultured Comparative Study DNA  Antisense Dose-Response Relationship  Drug ENDOTHELIN-1 Fibroblast Growth Factor 2 Gene Expression Regulation Muscle  Smooth  Vascular Oligonucleotides RNA  Messenger RATS Rats  Inbred SHR Rats  Inbred WKY Research Support  Non-U.S. Gov't Time Factors 

分 类 号：R965[医药卫生—药理学]