The Adverse Effect of Selective Cyclooxygenase-2 Inhibitor on Random Skin Flap Survival in Rats

BACKGROUND Cyclooxygenase-2(COX-2) inhibitors provide desired analgesic effects after injury or surgery, but evidences suggested they also attenuate wound healing. The study is to investigate the effect of COX-2 inhibitor on random skin flap survival. METHODS The McFarlane flap model was established in 40 rats and evaluated within two groups, each group gave the same volume of Parecoxib and saline injection for 7 days. The necrotic area of the flap was measured, the specimens of the flap were stained with haematoxylin-eosin(HE) for histologic analysis. Immunohistochemical staining was performed to analyse the level of VEGF and COX-2 . RESULTS 7 days after operation, the flap necrotic area ratio in study group (66.65 ± 2.81)% was significantly enlarged than that of the control group(48.81 ± 2.33)%(P <0.01). Histological analysis demonstrated angiogenesis with mean vessel density per mm(2) being lower in study group (15.4 ± 4.4) than in control group (27.2 ± 4.1) (P <0.05). To evaluate the expression of COX-2 and VEGF protein in the intermediate area II in the two groups by immunohistochemistry test .The expression of COX-2 in study group was (1022.45 ± 153.1), and in control group was (2638.05 ± 132.2) (P <0.01). The expression of VEGF in the study and control groups were (2779.45 ± 472.0) vs (4938.05 ± 123.6)(P <0.01).In the COX-2 inhibitor group, the expressions of COX-2 and VEGF protein were remarkably down-regulated as compared with the control group. CONCLUSION Selective COX-2 inhibitor had adverse effect on random skin flap survival. Suppression of neovascularization induced by low level of VEGF was supposed to be the biological mechanism.