| Objective: The effects of local delivery thalidomide on inhibiting neointimal hyperplasia and VEGFmRNA expression after balloon injury in rat carotid artery and possible mechanisms were researched in the present paper.Methods: 48 male Sprague-Dawley rats were randomly divided into sham operation group (group A), alone operation group (group B) and Thalidomide group (group C). The carotid arteries of group B and group C were injured by conventional Percutaneous transluminal coronary angioplasty (PTCA) balloon catheter, group C were treated by local delivery thalidomide and group B without delivery thalidomide, The arteries of group A were not injured. 7 days and 14 days after balloon injury, rats were sacrificed. Serum concentrations of vascular endothelial growth factor (VEGF) and tumor necrosis factor-α(TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). HE staining was performed to observe neointima area, lumen area. Macrophage infiltration and local expressions of VEGF were measured by immunohistochemical analyses. Real time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the expression of VEGFmRNA.Results:①Rat models of balloon injury and thalidomide local delivery by porous balloon were successfully completed. 7 days and 14 days after balloon injury ,the levels of VEGF and TNF-αwere more significantly increased in group B than that in group C (VEGF:4.82±0.17pg/ml vs 0.98±0.1pg/mL on day 7, P0.01;6.3±0.16pg/ml vs 1.03±0.09pg/mL on day 14, P<0.01; TNF-α:83±1.01pg/mL vs 76.37±0.75pg/mL on day 7, P0.01; 84.06±1.11pg/*mL vs 78.46±0.94pg/mL on day 14, P<0.01).②Morphometric analysis revealed no significant differences in the neointimal area of group C and B ((0.07±0.01mm~2 vs 0.13+0.02mm~2,P>0.05) and in lumen area of group A, B and C (B to A:0.33+0.03mm~2 vs 0.39±0.05mm~2,P>0.05; C to B: 0.39±0.04mm~2 vs 0.33+0.03 mm~2,P>0.05; C to A: 0.39±0.04mm~2 vs 0.39±0.05mm~2, P>0.05) 7 days after balloon injury. However, thalidomide administration resulted in a significant reduction of neointimal formation 14 days after balloon injury (0.07±0.01mm~2 in group C vs 0.12±0.04mm~2 in group B, P<0.01).therefore, lumen area was significantly decreased (0.31+0.03mm~2 in group B vs 0.4 +0.06mm~2 in group C, P<0.01).no significant differences present in the lumen area of group C and A (0.4+0.06mm~2 vs 0.4+0.08mm~2,P >0. 05).③VEGFmRNA expression levels were no statistic meaning in group A, B and C on 7 days (B to A: 1.04±0.09 vs 0.97±0.14, P>0.05;C to B: 0.98±0.1 vs 1.04±0.09, P >0.05; C to A: 0.98±0.1 vs 0.97±0.14, P>0.05). VEGFmRNA expression of injured arteries in Group B on 14 days was significantly increased compared with that in Group C and A (6.3±0.16 vs 1.03±0.09, P<0.01; 6.3±0.16 vs 0.90±0.11, P<0.05). However, there were no significant differences in group C and A(1.03±0.09 vs 0.90±0.11,P> 0. 05).④There were no differences of VEGF and macrophage staining among 3 groups on 7 days, the mean optical density values were respectively 0.1131±0.0112, 0.1034±0.0120, 0.1200±0.0136(P>0.05). VEGF staining was significantly increased in the nucleus and the cytoplasm of group B 14 days after balloon injury, which was attenuated in group C, the mean optical density values were 0.1784 + 0.0112 and 0.1234 + 0.0122(P<0.01). Tissue macrophage infiltration was significantly reduced in the group C compared with group B 14 days after balloon injury and the mean optical density values were 0.1084 + 0.0157 and 0.1837 + 0.0144 (P<0.01).Conclusions: The result shows that thalidomide using local drug delivery significantly reduced the levels of VEGF and TNF-αin serum, decreased macrophage infiltration and local protein content of VEGF and VEGFmRNA expression, inhibited neointimal hyperplasia and vascular restenosis after balloon injury in rat carotid artery, which suggests an essential role for VEGF in the pathogenesis of restenosis. This might provided a novel method for prevention and therapy of restenosis.
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