Effects And Molecular Mechanism Of Ursolic Acid On Proliferation Of Human Aortic Vascular Smooth Muscle Cells

Objective : To investigate the effects of Ursolic Acid on the proliferation of Human aortic vascular smooth muscle cells in vitro,discusses the relevance of GRIM-19/pSTAT3/Cyclin D1 to human aortic vascular smooth muscle cells proliferation,interpretation the possible mechanism of ursolic acid in human aortic vascular smooth muscle cells.Methods: The hyperlipidemia model was established,the cells was divided into: normal group,15% hyperlipidemia group,20% of hyperlipidemia,UA dosage groups(including10 ?M,including 20? M,including 30 ?M),CCK8 assay was performed to measure cell viability.Real-time RCR and Western blotting were used to investigate the m RNA and protein expression levels of GRIM-19,p-STAT3 and Cyclin D1 respectively.RNA interference and plasmid overexpression was applied to confirm the signaling pathway.Western blotting was used to measure the interference efficacy,target protein expression levels in normal,interference or overexpression.Results:1)CCK8 test showed that with 15% hyperlipidemia serum HASMC for 24 h can significantly increased the cell proliferation rate;with UA(10?M,20?M,30?M)for12h,the cell inhibition was significant respectively,the difference was statistically significant(P <0.05);2)The m RNA and protein expression levels of endogenous GRIM-19 in control group was significantly higher than that in model group(P<0.05);3)High expression of endogenous GRIM-19 in normal group at the same time with the low expression of p-STAT3 and Cyclin D1;Proliferation of endogenous GRIM-19 lower expression level at the same time with the elevated of p-STAT3 and Cyclin D1;4)Endogenous GRIM-19 protein expression is increased expression than in model group with UA impact;5)The expression of Cyclin D1 protein levels depressed with p-STAT3inhibitors;6)With the silence of GRIM-19,Cyclin D1 and p-STAT3 protein expression level increased(P<0.05);7)With the overexpression of GRIM-19,p-STAT3 and Cyclin D1 protein expression levels were significantly decreased(P<0.05).Conclusions: 1)Endogenous GRIM-19 protein was proved in HASMC;2)Endogenous GRIM-19 may have relationship with the proliferation of HASMC;3)UA play an importangt role in AS development may though elevated the expression of endogenous GRIM-19 in HASMC to inhibition p-STAT3 and Cyclin D1 with suppression the proliferation of HASMC.