The Function Of Caspase-8 And NF-κB Acted In Lung Injury Induced TNF-Alpha After Inchemia-reperfusion Of Small Intestinal

Intestine ischemia -reperfusion can cause systemic inflame- matory responses and multiple organ dysfunction syndromes. But the mechanism of multiple organ dysfunction syndrome damage such as lungs, liver, kidney is not clear so far induced by intestine ischemia reperfusion.Generating a great deal of oxidizing free radicals after intestine ischemia-reperfusion,and more neutrophile granulocyte being activated, inflammatory mediator created for example TNF-a and proteinase growing in number,all these can give rise to a series of chain reactions。TNF-αcan make neutrophile granulocyte gather together with lung endothelial cells, and this can lead to lung injury. On the same time, TNF-a can make Caspase-8 be activated, both of them can aggravate lung injury further more. During the time of ischemia -reperfusion a number of inactive NF-κB were activated. They can make positive feedback regulation with TNF-a, enhance its transcription and increase its number. Then they can cooperate with each other to urge generating a great deal of oxidizing free radicals and inflammatory mediator. The metabolites of them were accumulated in the lung alveolar epithelial cells, leading to appear lung structural modification and dysfunction, finally lung nonfunction.Objective:to observe the expression of Caspase-8 and NF-κB acted in lung type II alveolar epithelial cells induced by TNF-alpha after rat intestinal ischemia-reperfusion.Methods:48 male Wistar rats (8-12 weeks) weighing 200-250g were randomly divided into normal group, sham group, control group and the experimental group; and then establishing small intestine ischemia -reperfusion model; extracting materials of the lung typeⅡepithelial cells at 24 hours after ischemia-reperfusion; using histotherapy and immunohistochemical staining techniques and image analysis technology, to observe histopathological changes and the expression of Caspase-8 and NF-κB.Results:The masculine Caspase-8 lies in alveolar epithelial cell cytolymph, and its expression strength in the experimental group is higher than the control group, the sham group and the normal group (P<0.05).Positive expression of NF- kB lies in alveolar epithelial cell nuclei or cytolymph and its expression strength in the experimental group is higher than the control group, the sham group and the normal group (P<0.05).Conclusion:Caspase-8 and NF-κB which took part in the process of pathological changes during the apoptosis of lung epithelial cells caused by TNF alpha after the rats'intestinal ischemia-reperfusion injury. After lung injury, the value of Wet Dry ratio (W/D) was up. Both in the two sets of experiments, the value of W/D in the experiment group show that was higher than the normal group, the sham group and the control group. All that can prove the rats of the experiment group were injured more heavily in the lung injury.Our experiments indicated that the Caspase-8 and NF-KB had a high expression in the experiment rats'lung organizes.Which explained the two after being activated, all took part in lung injury induced by TNF- alpha after rat intestinal ischemia-reperfusion. And this can indicate they would take an important part in TNF alpha cell signaling pathways. So inhibiting its expression activity may reduce acute respiratory distress syndrome and multiple organ dysfunction syndromes which were caused by the mesenteric vascular ischemic diseases. But whether Caspase-8 and NF-KB have a relationship with each other we have no idea, and this will still need a further research.