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

Abstract

BackgroundCyclooxygenase-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.MethodsThe 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 .Results7 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 mm2 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.ConclusionSelective 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.

Inhibition of cyclooxygenase‐1 and ‐2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds

“…In line with our finding, two of the most recent studies again confirm that notion. Celecoxib severely disturbed skin repair in two distinct rodent models of acute wound healing; celecoxib interfered with regeneration of murine excisional wounds (16) as well as with the effective integration of skin flaps in rats (15). Together with the presented data, both studies argue that wound VEGF expression and angiogenesis were dependent on wound Cox-2 activity.…”

“…Nevertheless, the number of functional studies on the role of NSAIDs in acute cutaneous wound healing is very limited. Here, injury-induced Cox-2 was functionally related to wound impairments upon its selective inhibition, leading to disturbed re-epithelialisation, ECM formation, angiogenesis and myofibroblast differentiation (14)(15)(16). These findings are complemented by additional studies that emphasise the essential role of the keratinocyte-expressed, constitutive Cox-1 isoform for skin repair (10,11).…”

Experimental study of survival of pedicled perforator flap with flow-through and flow-end blood supply

“…VEGF is a heparin‐binding glycoprotein that stimulates vasculogenesis and angiogenesis in response to hypoxia in many cell lines. Hypoxia has a bidirectional modulatory effect on VEGF expression and neoangiogenesis.…”

Effects of diammonium glycyrrhizinate on random skin flap survival in rats: An experimental study

“…Group II and group III received 10 ml/kg DG via intraperitoneal injection once and twice per day, respectively, for 7 days. The control group was injected with the same quantity of saline solution in the same way once per day during the experiment (11). All rats were housed in a environmentally controlled room at a temperature of 20-22˚C under 12 h light/dark cycles.…”