Paeonol inhibits vascular smooth muscle cell proliferation by regulating proliferating cell nuclear antigen and P27kip1 expression / 中华老年医学杂志

ABSTRACT

Objective To study the preventive effect of paeonol on restenosis after angioplasty in rabbit balloon injury model and its mechanism.Methods Male New Zealand white rabbits with clean grade were selected.Balloon injury rabbit abdominal aorta combined with high cholesterol diet were used to establish rabbit atherosclerosis model.We used balloon to dilate the narrow abdominal aorta.The animals were randomly divided into four groups (control group,low concentration paeonol group,high concentration paeonol group and rapamycin group).Animals in different group were orally given normal saline 2 ml · kg-1 · d-1,low concentration of paeonol 75 mg · kg-1 · d-1,high concentration of paeonol 150 mg · kg-1 · d-1,rapamycin administrated with 1.25 mg · kg-1 · d-1 for six weeks respectively.After 6 weeks,the animals were killed by air embolism,and immediately dissected to remove the abdominal aorta.We used hematoxylin and eosin(HE) staining and Masson staining to detect the thickness of the arterial intimal hyperplasia and the gross morphological changes of the narrow artery.Immunohistochemical staining was used to detect changes of proliferating cell nuclear antigen (PCNA) expression level.Western blotting was used to discover P27kip1 protein expression in the narrow artery.Results Paeonol and rapamycin reduced the degree of intimal hyperplasia.The neointima areas in the control group,low concentration paeonol group,high concentration paeonol group and rapamycin group were (0.16±0.03),(0.09±0.01),(0.05±0.01) and (0.04±0.01) respectively; the ratio of neointimal area to media area was (90.62 ±3.43),(42.30 ±2.94) (33.72±3.19) and (28.78±6.67) respectively; the intimal area proliferation rate was (33.3 ± 3.1) ％,(23.2 ± 2.2) ％,(17.5 ± 1.5) ％ and (16.2 ± 1.7) ％ respectively.There were significant differences in the neointima area,ratio of neointimal area to media area,and the intimal area proliferation rate among the four groups (F=47.98,257.25,74.60,all P＜0.05).The expression level of PCNA and P27kip1 protein were (0.20±0.04),(0.06±0.02),(0.05±0.02) and (0.08± 0.02),and (0.47±0.09),(0.78±0.20),(1.29±0.12) and (1.83±0.13) in the control group,low concentration paeonol group,high concentration paeonol group and rapamycin group respectively,and the differences were statistically significant between the four groups (F=37.22 and 107.69,both P＜0.01).Conclusions Paeonol plays a role in anti-vascular smooth muscle cell proliferation.This effect may be through inhibiting the expression of PCNA,and increasing the expression of P27kip1 in the cell cycle.