A salvianolic acid B-rich fraction of Salvia miltiorrhiza induces neointimal cell apoptosis in rabbit angioplasty model

Apoptosis has been suggested to participate in stabilizing cell number in r estenosis. Salvia miltiorrhiza (SM) Bunge which is a Chinese herb widely us ed for the treatment of cardiovascular disorders contains a potent antioxid ant, Salvianolic acid B. To determine whether the antioxidant affects vascu lar apoptosis, the present study examined the frequency of apoptotic cell d eath in atherosclerotic plaques and in restenotic lesions of cholesterol-fe d rabbits. New Zealand White rabbits were treated with a normal diet (norma l), a 2% cholesterol diet (HC), a 2% cholesterol diet and endothelial denud ation (HC-ED), a 2% cholesterol diet with 5% water-soluble extract of SM (4 .8 g/Kg B.W./day) and endothelial denudation (HC-ED-SM), or with a 2% chole sterol diet containing probucol (0.6 gikg B.W./day) and endothelial denudat ion (HC-ED-probucol). Apoptosis and associated cell types were examined in serial paraffin sections by in situ terminal deoxynucleotidyl transferase-m ediated dUTP nick end labeling and immunohistochemistry. The expression of p53, an apoptosis-related protein, was also examined. Apoptosis was mainly detected in the neointima of the three groups with endothelial denudation. The percentage of apoptotic cells in SM-treated group (68.5+/-5.9%) was sig nificantly higher than that of normal (0%), HC (1.9+/-1.2%), HC-ED (46.1+/- 5.4%), and probucol-treated (32.8+/-3.9%) groups. The SM treatment markedly reduced the thickness of the neointima which was mainly composed of smooth muscle cells with few macrophages. In accordance with the apoptotic cell c ounts, positive immunoreactivity for p53 was observed in restenotic lesions from HC-ED, SM-treated and probucol-treated groups but not in the intima o f the other two groups. These results suggest that the treatment with salvi anolic acid B-rich fraction of SM induces apoptosis in neointima which in t urn may help prevent the neointimal thickening.