摘要
AIM:To investigate whether tumor necrosis factor-α(TNF-α)mediates ischemia-reperfusion(I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase(JNK)activation.METHODS:In this study,intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion,and the rats were pretreated with a TNF-α inhibitor,pentoxifylline,or the TNF-α antibody infliximab.After surgery,part of the intestine was collected for histological analysis.The mucosal layer was harvested for RNA and protein extraction,which were used for further real-time polymerase chain reaction,enzyme-linked immunosorbent assay and Western blotting analyses.The TNF-α expression,intestinal mucosal injury,cell apoptosis,activation of apoptotic protein and JNK signaling pathway were analyzed.RESULTS:I/R significantly enhanced expression of mucosal TNF-α at both the mRNA and protein levels,induced severe mucosal injury and cell apoptosis,activated caspase-9/caspase-3,and activated the JNK signaling pathway.Pretreatment with pentoxifylline markedly downregulated TNF-α at both the mRNA and protein levels,whereas infliximab pretreatment did not affect the expression of TNF-α induced by I/R.However,pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling.CONCLUSION:The results indicate there was a TNFα-mediated JNK activation response to intestinal I/R injury.
AIM:To investigate whether tumor necrosis factor-α(TNF-α)mediates ischemia-reperfusion(I/R)-induced intestinal mucosal injury through c-Jun N-terminal kinase(JNK)activation.METHODS:In this study,intestinal I/R was induced by 60-min occlusion of the superior mesenteric artery in rats followed by 60-min reperfusion,and the rats were pretreated with a TNF-α inhibitor,pentoxifylline,or the TNF-α antibody infliximab.After surgery,part of the intestine was collected for histological analysis.The mucosal layer was harvested for RNA and protein extraction,which were used for further real-time polymerase chain reaction,enzyme-linked immunosorbent assay and Western blotting analyses.The TNF-α expression,intestinal mucosal injury,cell apoptosis,activation of apoptotic protein and JNK signaling pathway were analyzed.RESULTS:I/R significantly enhanced expression of mucosal TNF-α at both the mRNA and protein levels,induced severe mucosal injury and cell apoptosis,activated caspase-9/caspase-3,and activated the JNK signaling pathway.Pretreatment with pentoxifylline markedly downregulated TNF-α at both the mRNA and protein levels,whereas infliximab pretreatment did not affect the expression of TNF-α induced by I/R.However,pretreatment with pentoxifylline or infliximab dramatically suppressed I/R-induced mucosal injury and cell apoptosis and significantly inhibited the activation of caspase-9/3 and JNK signaling.CONCLUSION:The results indicate there was a TNFα-mediated JNK activation response to intestinal I/R injury.
基金
Supported by Grants-in-Aid from the Major Projects Incubator Program of the National Key Basic Research Program of China,No. 2012CB526700
National Natural Science Foundation of China,No. 30971357
Natural Science Foundation of Guangdong Province,No. S2011020002348
Science and Technology Planning Project of Guangdong Province,No. 2009B060300001
Major Projects Incubator Program of SunYat-Sen University,No.10ykjc25
