<正> Objective To study the potential role of tumor necrosis factor-or(TNF-α)induction in the development ofmucosal barrier dysfunction in rats caused by acute intestinal ischemia-reperfusion injury,and to examine whetherpretreatment with monoclonal antibody against TNF-α(TNF-αMoAb)would affect the release of D(-)-lactate afterlocal gut ischemia followed by reperfusion.Methods Anesthetized Sprague-Dawley rats underwent superiormesenteric artery occlusion for 75 min followed by reperfusion for 6 hr.The rats were treated intravenonsly with eitherTNF-α MoAb(20 mg/kg)or albumin(20 mg/kg)30 min prior to the onset of ischemia.Plasma D(-)-lactate levelswere measured in both the portal and systemic blood by an enzymatic spectrophotometrie assay.Intestinal TNF-αmRNA expression as well as protein levels were also measured at various intervals.In addition,a postmortemexamination was performed together with a macropatholngical evaluation based on a four-grade scoring system.Results Intestinal ischemia resulted in a significant elevation in D(-)-lactate levels in the portal vein blood in boththe control and treatment groups(P<0.05).However,animals pretreated with TNF-α MoAb at 6 hr after reperfusionshowed significant attenuation of an increase in both portal and systemic D(-)-lactate levels when compared with thoseonly receiving albumin(P<0.05).In the control animals,a remarkable rise in intestinal TNF-α level was measuredat 0.5 hr after clamp release(P<0.01);however,prophylactic treatment with TNF-α MoAb completely annulled theincrease of local TNF-α levels seen in the control animals.Similarly,after anti-TNF-α MoAb administration,intestinalTNF-α mRNA expression was markedly inhibited,which showed significant differences when compared with the controlgroup at 0.5 hr,2 hr and 6 hr after the release of occlusion(P<0.05-0.01).In addition,the pathologicalexamination showed marked intestinal lesions that formed during ischemia,which were much worse upon reperfusion,particularly at the 6 hr time point.These acute injuries were obviously attenuated in animals receiving TNF-α MoAb.Conclusions It appeared that acute intestinal ischemia was associated with failure of the mucosal barrier,resulting inincreased plasma D(-)-lactate levels in both portal and systemic blood.These results suggest that TNF-α appears to beinvolved in the development of local damage associated with intestinal ischemic injury.Moreover,prophylactictreatment with TNF-α MoAb exerts preventive effects on ischemia/reperfusion-induced circulating D(-)-lactateelevation and gut injury.(J Geriatr Cardiol 2004;1(2):119-124.)
