Time course of COX-1 and COX-2 expression during ischemia-reperfusion in rat skeletal muscle

1 Unité Mixte de Recherche 181 de Physiopathologie et Toxicologic Expérimentales, Institut National de la Recherche Agronomique/Ecole Nationale Vétérinaire de Toulouse, Toulouse; and 2 Departement de Pathologic, Centre Hospitalier Universitaire de Rangueil, Toulouse, France Submitted 28 June 2004 ; accepted in final form 20 September 2005 The aim of this study was to assess cyclooxygenase (COX)-1 and COX-2 expression in skeletal muscle after an ischemia-reperfusion (I/R). Male Sprague-Dawley rats were subjected to unilateral hindlimb ischemia for 2 h and then euthanized after 0, 1, 2, 4, 6, 10, 24, and 72 h of reperfusion. The COX protein and mRNA were assessed in control and injured gastrocnemius muscle. Muscle damage was indirectly determined by plasma creatine kinase activity and edema by weighing wet muscle. Creatine kinase activity in plasma increased as early as 1 h after reperfusion and returned to control levels by 72 h of reperfusion. Edema was observed at 6 and 10 h of reperfusion, but histological investigations showed an absence of tissular inflammatory cell infiltration. COX-1 mRNA was expressed in control muscle and was increased at 72 h of reperfusion, but the levels of associated COX-1 protein detected in control and injured gastrocnemius muscle were similar. COX-2 mRNA was not, or only slightly, detectable in control muscle and after I/R. In contrast, I/R induced major overexpression of COX-2 immunoreactivity at 6 and 10 h of reperfusion with a maximum at 10 h, whereas COX-2 protein was undetectable in control muscle. In conclusion, hindlimb I/R induced a large overexpression of COX-2 but not COX-1 protein between 6 and 10 h after injury. These results suggest a role for COX-2 enzyme in such pathophysiological conditions of the skeletal muscle. cyclooxygenase; skeletal muscle injury; inflammation Address for reprint requests and other correspondence: V. Dupouy, UMR 181 Experimental Pathophysiology and Toxicology INRA/ENVT, 23 chemin des Capelles, BP 87614, 31 076 Toulouse cedex 03, France (e-mail: v.dupouy{at}envt.fr )