Roles of cyclooxygenase-2 in tissue injury during hemorrhagic shock.
Prostaglandins (PGs), which play a pivotal role in the cytokine network, have been implicated in the pathophysiology of circulatory shock, but the precise role of cyclooxygenase-2 (COX-2) in circulatory shock is still not known. This study investigated whether or not COX-2 affects liver and bowel injury during hemorrhagic shock (HS). Male Sprague-Dawley rats were subjected to decompensated HS followed by resuscitation. Besides the time course of tissue injury and mRNA expression of COX-2 in the liver and bowel during HS, we investigated the effect of N-(2-cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS398), a specific inhibitor of COX-2, on injury to these organs. The liver injury, evaluated by plasma aminotransferase levels and histology, was evident at the end of the shock period (Shock-0h) and had significantly increased 1 h after the start of resuscitation (Shock-1h) (P < 0.01). The bowel injury, assessed by histological findings in the terminal ileum, was scarcely detectable at Shock-0h but became noticeable at Shock-1h (P < 0.01). COX-2 mRNA expression was up-regulated in the liver during HS whereas it did not change in the bowel. NS398 treatment significantly exacerbated both liver and bowel injury. These lines of evidence suggest that COX-2-derived PGs provide protection against HS-induced liver and bowel injury.
Tsukada
K
K
First Department of Surgery, Gunma University School of Medicine, Japan.
Hasegawa
T
T
Tsutsumi
S
S
Kuwano
H
H
D000199:Actins / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D007422:Intestines / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000293:injuries* / Q000473:pathology; D008297:Male; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors
D000199:Actins; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D017931:DNA Primers; D007527:Isoenzymes; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases