Effects of glycyrrhetic acid on the expression of c-fos mRNA and cell proliferation in rat vascular smooth muscle cells / 中国药理学通报

ABSTRACT

AIM To analyze the effects of glycyrrhetic acid (GA) on c-fos expression and cell proliferation in rat vascular smooth muscle cell (VSMC), and to figure out the mechanisms of binding GA to angiotensin Ⅱ(AⅡ) receptor. METHODS Primary cell culture of rat VSMC, Northern blot, TdR incorporation DNA assay and MTT assay were used in this study. RESULTS ① GA at both low (1?10 -9 mol?L -1) and high concentration (1?10 -5 mol?L -1) quickly induced c-fos expression in VSMC. Sar-AⅡ(1?10 -5 mol?L -1)inhibited both GA induced and AⅡ (1?10 -5 mol?L -1) induced c-fos expression. GA enhanced AⅡ induced c-fos expression at both low and high concentration in VSMC. ② Low level of GA stimulated the proliferation of VSMC. This stimulatory effect decreased with increasing GA concentration, and changed to be inhibitory at high concentration of GA. Not only did Sar-AⅡ eliminate the stimulatory effect of low concentration of GA on cell proliferation, it also eliminated the inhibitory effect of high concentration of GA. Low concentration of GA enhanced the stimulation of AⅡon cell proliferation, while the inhibitory effect of high concentration of GA on cell proliferation was relieved by adding 1?10 -7 mol?L -1 AⅡ. CONCLUSION This study suggests that GA activates transcription factor c-fos and promotes the proliferation of VSMC. GA may exert its effects on cells through AT 1 receptor since it induces similar changes as AⅡ and its effects can be inhibited by AT 1 receptor antagonist.