Intestinal Ischemia-reperfusion Injury, Intestinal - Lymph Channels "active Substance Identification And Nutrition Intervention Study

Background:Intestinal tract is the central organ of stress.Intestinal ischemia/reperfusion(I/R) injury plays an important role in the development and prognosis of severe trauma,extensive burns,shock,major surgery,which may even lead to systemic inflammatory response syndrome(SIRS) and multiple organ dysfunction syndrome(MODS).However,the mechanism intestinal ischemia/reperfusion(I/R) injury causing remote tissues and organs injuries has not been well understood.And there is not effective means of prevention and treatment yet.Objective:The purposes of this study is to investigate the influence on lung,intestine and systemic inflammation when blocking the "gut-lymph pathway" by setting up a method for drainage of rat lymph fluid.Then lymph fluid of I/R group was applied to stimulate macrophage to investigate the possible mechanism of some active materials in lymph fluid.Besides,some EPA was applied to macrophage to observe whether the nutritional intervention was effective.Results:Intestine,liver,kidney and lung were injuried after intestinal ischemia for 60 minutes and reperfusion for 120 minutes.The expression of HMGB1 was significantly increased.Endotoxin,HMGB1 and cytokines such as TNF-α,IL-1,IL-6 were also significantly increased,and the intestinal mucosal was damaged.The 'gut-lymph pathway' could be blocked by drainage of lymph fluid,which could relieve injury of intestine,attenuate injury of intestine mucosa,liver,lung,kidney,and would reduce the systemic inflammatory response.There were many proinflammatary factors in lymph fluid of ischemia-reperfusion group,some of which was endotoxin;others would be some inflammatory mediators such as TNF-α,IL-1,IL-6 and HMGB1,which all irriated the activation and injury of macrophage.When EPA was applied to cell culture medium, the injury of macrophage suffering from lymph fluid of ischemia-reperfusion group was reduced significantly.The expression of HMGB1 and inflammatory factors were also reduced significantly(the P value is＜0.05).It indicated that nutritional intervention would be protective to some extent in the injury caused by endotoxin or HMGB1.Conclusions After intestine ischemia-reperfusion,the intestine mucosa was injured and the expression of HMGB1,endotoxin and cytokines were increased significantly. Drainage of lymph fluid could relieve the injury of remote tissues and organs,such as intestine,liver,lung and kidney.The application of EPA could relieve the injury of macrophage caused by lymph fluid of ischemia reperfusion injury.Intestinal I/R injury causing remote tissues and organs injuries will be related to some active factors in gut lymph fluid."Gut-lymph pathway" built a bridge between inflammatory factors(such as HMGB1 and endotoxin) and remote organ injury.Blocking the gut-lymph pathway would relieve the injury of lung or reduce systemic inflammation.In these inflammatory factors(either HMGB1 or endotoxin),which were more important was still indistinct. The application of nutritional intervention and(or) blocking gut-lymph pathway could provide a reference in treatment of such diseases in future.