Effects of All-trans Retinoic Acid on Expression of P16 and Proliferation Cell Nuclear Antigen after Thoracic Aorta Balloon Injury in Rats

Aim To investigate the effects of all-trans retinoic acid (ATRA) on intimal proliferation, expression of suppressor gene P16 and proliferation cell nuclear antigen (PCNA)after vascular injury in rats. Methods Rats were randomly divided into three groups: Group 1(n=24) were given vascular balloon injury, Group 2 (n=24) were given 30 mg/(kg·d) ATRA into stomach from 4 days before injury to 28 days after injury, Group 3 (n=6)served as controls were killed at 14th day after operation. Neointima area were calculated morphologically at day 14, 28 after injury. The expression of P16 and PCNA were measured by means of immunohistochemical technique and imagine analyzer at day 2, 7, 14, and 28 after injury. Results The migration and proliferation of vascular smooth muscle cells(VSMC) had not existed at day 2 after balloon injury in control group. The thickening of intima had begun at day 7 after injury,and they were more significant at day 14. The proliferation of vascular smooth muscle cells decreased at day 28,but extracellular matrix increased and the intimal thickning continued. The positive expression of PCNA were found at day 2 and reached maximum at day 7 and begun decreasing at day 14 after balloon injury, but the expression changes of P16 was inapparent when given ATRA, the neointimal area and the index of PCNA expression reduced at every time point,but the expression of P16 begun increasing at day 2 and reached maximum at day 14 after vascular balloon injury. Conclusion ATRA can effectively repress intimal proliferation after vascular injury, which may be associated with inhibting the proliferation of vascular smooth muscle cells through down-regulating the expression of PCNA and upregulating that of P16.