摘要
Abstract Objective To test the hypothesis that in a rat model of acute intestinal ischemia/reperfusion injury, endotoxemia from the gastrointestinal tract would play a role in mediating tumor necrosis factor (TNF) response and remote organ dysfunction. Methods Wistar rats underwent 45 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion. The rats were treated intravenously with either TNF monoclonal antibody (MoAb) or saline solution 90 minutes prior to the onset of ischemia. Results Significant elevation of plasma TNF level in both portal and systemic circulation was detected immediately after the onset of reperfusion. The level peaked at two hours after reperfusion (P<0.01). Similarly, a remarkable TNF mRNA expression in the intestine in controls was detected at 0.5 hour post reperfusion, and sustained a marked elevation throughout the observation period (P<0.05-0.01). TNF elevation was found associated with gut origin endotoxemia, and the maximal TNF response occurred approximately 0.5-2 hours after the initial appearance of endotoxin in the portal vein. Concomitantly, multiple organ dysfunction in response to local ischemic insult was also observed in untreated controls upon reperfusion, but it was significantly attenuated by pretreatment with MoAb against TNF. Conclusions Intestinal injury can result in the gut becoming a cytokine liberating organ. The escape of endotoxin and bacteria from the gut may be responsible for the TNF expression and release, which would be an important mechanism underlying pathophysiological alterations associated with intestinal ischemia/reperfusion injury.
Abstract Objective To test the hypothesis that in a rat model of acute intestinal ischemia/reperfusion injury, endotoxemia from the gastrointestinal tract would play a role in mediating tumor necrosis factor (TNF) response and remote organ dysfunction. Methods Wistar rats underwent 45 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion. The rats were treated intravenously with either TNF monoclonal antibody (MoAb) or saline solution 90 minutes prior to the onset of ischemia. Results Significant elevation of plasma TNF level in both portal and systemic circulation was detected immediately after the onset of reperfusion. The level peaked at two hours after reperfusion (P<0.01). Similarly, a remarkable TNF mRNA expression in the intestine in controls was detected at 0.5 hour post reperfusion, and sustained a marked elevation throughout the observation period (P<0.05-0.01). TNF elevation was found associated with gut origin endotoxemia, and the maximal TNF response occurred approximately 0.5-2 hours after the initial appearance of endotoxin in the portal vein. Concomitantly, multiple organ dysfunction in response to local ischemic insult was also observed in untreated controls upon reperfusion, but it was significantly attenuated by pretreatment with MoAb against TNF. Conclusions Intestinal injury can result in the gut becoming a cytokine liberating organ. The escape of endotoxin and bacteria from the gut may be responsible for the TNF expression and release, which would be an important mechanism underlying pathophysiological alterations associated with intestinal ischemia/reperfusion injury.
