内皮素-1对大鼠血管平滑肌表型转化和增殖的影响

Effect of endothelin-1 on the proliferation and phenotypic transformation of vascular smooth muscle cells in rat

目的:通过内皮素-1作用于大鼠血管平滑肌细胞(VSMC)及对内皮素-1受体信号的阻断,探讨内皮素-1对VSMC表型转化和增殖的影响及机制。方法:取大鼠主动脉贴块培养VSMC,用内皮素-1及其受体阻断剂BQ123分别作用于一般培养的VSMC和血清饥饿培养的VSMC。用BrdU标记细胞增殖;RT-PCR检测高血压相关基因-1(HRG-1)和SM22α表达变化。结果:内皮素-1作用后VSMC增殖显著增多,HRG-1和SM22αmRNA在一般培养和饥饿培养的VSMC中表达均明显减少;而加入阻断剂BQ123后增殖细胞大大减少,HRG-1和SM22αmRNA表达明显上调。结论:内皮素-1有促进VSMC增殖作用并可使VSMC从收缩型向合成型转化,并且内皮素-1对VSMC的作用是不可逆的;受体信号途径是内皮素-1对VSMC表型转化和增殖作用的机制之一。

Objective： To investigate the effect of endothelin-1 （ET-1） on the proliferation and phenotypic transformation of vascular smooth muscle cells （VSMC） and the mechanisms underlying this effect. Methods： VSMC were isolated from the rat abdominal aorta. VSMC cultured in both serum-containing or in a serum-free medium were treated with ET-1, ET-1 receptor agonist （BQ123） and various combinations of these factors. VSMC proliferation was determined by bromodeoxyuridine （BrdU） assays. The mRNA expression levels of HRG-1 and SM22α were determined by reverse transcription-polymerase chain reaction （RT-PCR）. Results： The proliferous .cells labeled by BrdU of cultured with ET-1 were increased and the mRNA expression of HRG-1 and SM22α was decreased. While the VSMC were cultured into the culture medium containing ET-1 receptor agonist （BQ123）, the proliferous cells labeled by BrdU were obviously decreased and the mRNA expression of HRG-1 and SM22α was significantly increased. Conclusion： ET- 1 can notably promote the proliferation of VSMC and nonreversibly change the VSMC from contractile to synthetic phenotype, which may be related to receptor signaling pathway.