血管紧张素Ⅱ促高血压大鼠血管平滑肌细胞增殖机制的研究

Mechanisms by which angiotensin II stimulates the proliferation of cultured aortic smooth muscle cells from spontaneously hypertensive rats

本工作以培养的正常血压WKY大鼠主动脉平滑肌细胞(ASMC)为对照,探讨血管紧张素Ⅱ(AngⅡ)对培养的SHR ASMC促增殖的机制.结果表明:AngⅡ(10^(-9)～10^(-6)mol/L)对SHR和WKY大鼠的ASMC均有促增殖作用且随剂量增加其作用加强,但对SHR ASMC的促增殖效应明显高于WKY大鼠.应用碱性成纤维细胞生长因子(bFGF)单克隆抗体(A-bFGF)和反义bFGF mR-NA均可明显抑制AngⅡ促SHR ASMC的增殖效应.此外,基础状态下及AngⅡ(10^(-6)mol/L)刺激8h后,SHR ASMC的bFGF基因表达均明显高于WKY大鼠.提示,AngⅡ的促细胞增殖作用部分是通过先诱发bFGF的产生而引起.

The present study is to elucidate mechanisms by which angiotensin II (Angll) stimulates the proliferation of cultured aortic smooth muscle cells (ASMC) from spontaneously hypertensive rats (SHR) as compared with normotensive Wistar-Kyoto (WKY) rats. Our results demonstrated that Ang II (10^(-9)-10^(-9) mol/ L) markedly stimulated SHR and WKY rats ASMC proliferation in dose-dependent manner. Both anti-basic fibroblast growth factor (bFGF) antibody (l0μg/ ml) and antisense bFGF mRNA (5 μmol/L) obviously inhibited Ang II-stimulated SHR ASMC proliferation. Moreover, both in basal and Ang II stimulated states, levels of bFGF gene expression in SHR ASMC were higher than those in WKY rats'. These results indicated that Ang II-induced bFGF production is one of the mechanisms by which Ang II stimulates SHR ASMC proliferation.