THE Effects And Mechanism Of Probucol And Fu Fang Dan Shen Drops Alone And In Combination On Frequency Of Experimental Restenosis

Objective To explore the effects and mechanism of Probucol and Fu Fang Dan Shen Drops alone and in combination on frequency of experimental restenosis.Methods 40 male rabbits (body weight 2000g～2300g) were balloon injuried on the iliac artery after 2 weeks of a high-cholesterol diet (2g Cholesterol and 6g peanut oil/day ), then were randomly assigned to one of four groups:probucol(1g/day, n=10), Fu Fang Dan Shen Drops (300mg/day, n=10), combination (n=10), and control (no drug, n=10). Each group administered drugs for 3 days before and was continued until the rabbits were killed 4 weeks after balloon injury. Morphometric analysis of the injured arteries included the intimal area (square millimeters), internal elastic lamina(IEL)area (square millimeters), and extral elastic lamina(EEL)area(square millimeters). The vascular endothelial growth factor(VEGF)and proliferating cell nuclear antigen(PCNA) protein level in neointimal were studied by means of immunohistochemistry.Result ①The neointimal area of probucol group was less than that of control group(0.31±0.17mm2 vs 0.58±0.14 mm2,P<0.05),however,the IEL area was larger than that of control group(1.36±0.19 mm2 vs 1.18±0.21 mm2, P<0.05). Compared with control group, the neointimal area of Fu Fang Dan Shen Drops group was decreased (0.33±0.21mm2 vs 0.58±0.14mm2, P<0.05). There was not significant difference between combination group and probucol or Fu Fang Dan Shen Drops group in the neointimal area but IEL area was larger. ② The level of PCNA protein was decreased significantly in drug treating groups, however, there was not difference between combination group and other two treating groups. ③The increased production of VEGF were found in proliferation intima of all groups. The level of VEGF protein correlated positively to neointimal area(r=0.75,P=0.04). ④The level of VEGF was lower in drug treating groups than in control group. Conclusion The therapy of probucol or Fu Fang Dan Shen Drops can reduced the rabbit iliac artery neointimal hyperplasia induced by ballon injury by decreasing The level of PCNA , perhaps the inhibition of VEGF expression in neointima is one of the mechanisms. Also probucol can improve vascular remodeling. Combining probucol with Fu Fang Dang Shen Drops can achieve improvement in vascular remodeling more than use alone.