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目的 研究甘草次酸 (GA)对大鼠血管平滑肌细胞(VSMC)原癌基因c fosmRNA表达及细胞增殖的影响 ,探讨GA与血管紧张素Ⅱ (AⅡ )受体结合的可能机制。方法 原代培养大鼠血管平滑肌细胞 ,[3H]TdR参入DNA、MTT分析法、Northernblot。结果 ①低浓度GA( 1× 10 -9mol·L-1)及高浓度GA( 1× 10 -5mol·L-1)均能导致c fosmRNA迅速表达 ;1× 10 -5mol·L-1Sar AⅡ能够阻断AⅡ、GA诱导的VSMCc fos表达 ;低浓度和高浓度GA都能促进AⅡ ( 1× 10 -5mol·L-1)诱导的VSMCc fos表达 ;②低浓度GA对细胞的增殖有促进作用 ;随着浓度的升高 ,促增殖作用减弱 ;高浓度GA抑制细胞的增殖。Sar AⅡ单独作用于VSMC ,不影响细胞增殖 ;Sar AⅡ能够阻断AⅡ对细胞增殖的促进作用 ;Sar AⅡ既抑制低浓度GA促细胞增殖作用 ,也消除高浓度GA抑制细胞增殖作用 ;低浓度GA与AⅡ联合作用 ,对细胞增殖的促进作用更加显著 ;高浓度GA与AⅡ联合作用于VSMC ,则可减轻高浓度GA对细胞增殖的抑制作用。结论 GA能激活c fos转录因子 ,从而产生对VSMC的增殖作用 ,因此 ,GA具有AT1受体的激动剂2 0 0 2 0 4 0 3收稿 ,2 0 0 2 0 7 2 3修回作者简介 :张凤云 ,女 ,33岁 ,硕士 ;贺师鹏 ,男 ,67岁 ,教授。研究方向 :酶和受体的拮抗剂样作用
Objective To investigate the effect of glycyrrhetinic acid (GA) on the expression of proto-oncogene c fos mRNA and cell proliferation in rat vascular smooth muscle cells (VSMC) and to explore the possible mechanism of GA binding to angiotensin II (AII) receptor. Methods Rat vascular smooth muscle cells were cultured in primary culture, and [3H]TdR was incorporated into DNA, MTT assay, and Northern blot. Results 1 Low concentration of GA (1 × 10 -9 mol·L-1) and high concentration of GA (1 × 10 -5 mol·L-1) all resulted in rapid expression of c fos mRNA; 1 × 10 -5 mol·L -1 Sar A II was able to Blocking AII, GA-induced VSMCc fos expression; low and high concentrations of GA can promote AII (1 × 10 -5mol · L-1)-induced VSMCc fos expression; 2 low concentrations of GA on the proliferation of cells can promote; With the increase of the concentration, the proliferative effect was weakened; the high concentration of GA inhibited the cell proliferation. Sar AII acts alone on VSMC without affecting cell proliferation; Sar AII can block the effect of AII on cell proliferation; Sar AII both inhibits the proliferation of cells with low concentration of GA and eliminates the effect of high concentration of GA on cell proliferation; low concentration of GA Combined with AII, the promotion of cell proliferation is more significant; high concentrations of GA and AII in combination with VSMC, can reduce the high concentration of GA inhibition of cell proliferation. Conclusion GA can activate the c fos transcription factor, resulting in the proliferation of VSMC. Therefore, GA has an AT1 receptor agonist 2020 0 4 0 3 Received, 20 20 2 0 7 2 3 : Zhang Fengyun, female, 33 years old, master degree; He Shipeng, male, 67 years old, professor. Research direction: Antagonist-like effects of enzymes and receptors