Effects of Ligustrazine on Inhibiting VSMCs Proliferation Induced by Angiotensin II Through Calcineurin Signal Pathway

Objective To explore the inhibiting effects of Ligustrazine on the proliferation of vascular smooth muscle cells (VSMCs) induced by angiotensin Ⅱ(AngⅡ)and study its mechanism from calcineurin signal pathway. Methods Cultured cells proliferating model of rats'VSMCs were established by AngⅡ. There were five groups:control group,AngⅡgroup,AngⅡand Ligustrazine (low dose,middle dose,high dose)respectively. Calmodulin(CaM)and calcineurin(CaN)activities were determined by enzyme reaction phosphorus measurement. MTT colorimetric assay was used to measure the proliferation of VSMCs. The expression of intranuclear proto-oncogenes c-myc and proliferating cell nuclear antigen(PCNA)were observed by immunocytochemical stain and imageanalysis technique. Results AngⅡ increased the proliferation activity, CaM or CaN activities and the expression of c-myc or PCNA with marked statistical difference comparing with the control group(P 0.05 or P 0.01). While the VSMCs were incubated with Ligustrazine in different doses[low dose(40 mg /L),middle dose (400 mg /L), high dose (4000 mg /L)] at the same time, the indexes above were obviously reduced comparing with AngⅡ group (P 0.05 or P 0.01). Conclusion The proliferation of rat VSMCs induced by AngII can be inhibited by Ligustrazine significantly,and the inhibiting mechanism of Ligustrazine may be related to inhibiting CaM or CaN activities, and then restraining the expressions of c-myc or PCNA in a dose and time-dependent manner.