黄芪和当归对血管平滑肌细胞表型标志基因表达和细胞增殖的影响

Effects of Astragalus Membranaceus and Angelica Sinensis on Phenotypic Modulation and Proliferation of Vascular Smooth Muscle Cells

为了观察黄芪和当归对血管平滑肌细胞表型转化和增殖的影响 ,采用体外培养的血管平滑肌细胞 ,以碱性成纤维细胞生长因子诱导其表型转化和增殖 ,在此基础上 ,通过Northern和Western印迹法检测平滑肌细胞表型标志基因表达的变化 ,研究黄芪和当归注射液对碱性成纤维细胞生长因子上述效应的抑制作用。结果发现 ,碱性成纤维细胞生长因子可明显下调分化型标志基因平滑肌α 肌动蛋白的表达 ,上调去分化型标志基因平滑肌胚胎型肌球蛋白重链和骨桥蛋白表达 ,诱导原癌基因c jun表达及促进血管平滑肌细胞DNA合成。黄芪和当归可上调分化型标志基因的表达活性 ,下调去分化型标志基因的表达 ,不同程度地抑制碱性成纤维细胞生长因子诱导的血管平滑肌细胞表型转化和DNA合成 ,有效抑制血管平滑肌细胞增殖 ,其作用机制可能与抑制碱性成纤维细胞生长因子诱导的c jun基因表达有关。二者相比 ,当归的作用大于黄芪。结果提示 ,黄芪和当归可从多位点上拮抗碱性成纤维细胞生长因子促血管平滑肌细胞表型转化及细胞增殖。

Aim To explore the effects of Astragalus membranaceus and Angelica sinensis on vascular smooth muscle cell (VSMC) phenotypic modulation and proliferation. Methods Basic fibroblast growth factor (bFGF) was used as a stimulus and the effects of Astragalus membranaceus and Angelica sinensis on VSMC differentiation, DNA synthesis and proto-oncogene expression in VSMC induced by bFGF were observed. Results bFGF could downregulate the expression of smooth muscle (SM) α-actin, induce the expression of smooth muscle embryonic myosin heavy chain and osteopontin, stimulate the expression of c-jun gene and promote the DNA synthesis. Both Astragalus membranaceus and Angelica sinensis could inhibit VSMC phenotypic modulation and DNA synthesis induced by bFGF, and result in the effective inhibition of VSMC proliferation. The mechanisms were related with the inhibition of c-jun gene expression stimulated by bFGF. Compared with Astragalus membranaceus, Angelica sinensis was more effective in inhibiting the VSMC phenotypic conversion and proliferation. Conclusions All results above reflected multi-site effects of Astragalus membranaceus and Angelica sinensis on VSMC phenotypic conversion and proliferation, and revealed their new pharmacological mechanisms.