Analyse des protektiven Effekts der Endotoxinpräkonditionierung am Pankreas mittels DNA-Chiptechnologie

Recently we demonstrated a protective effect of endotoxin preconditioning 24 h before pancreatic ischemia/reperfusion injury. In other organs the same effect has also been described. Mechanisms and responsible gene regulation are poorly investigated. We performed a study to investigate differential gene expression in the rat pancreas in the time course of endotoxin pre-treatment. Male wistar rats (5 groups, n = 5 animals/group) were pre-treated with 1 mg/kg KG endotoxin intraperitoneally. After 30 min, 3 h and 24 h, the pancreas was removed. Untreated animals and animals with injection of saline served as controls. After RNA isolation RNA was pooled and hybridised to Affymetrix chips to investigate 7 000 genes and 1000 ESTs. 3 h after administration of endotoxin there was an activation of proinflammatory transcription factors and other proinflammatory genes. After 24 h there was a clear decrease of these proinflammatory genes but a remaining and increasing up-regulation of important anti-apoptotic genes, anti-proteases and other probably protective genes. There was also a significant up-regulation of complement factors. Surprisingly heat-shock proteins and other typical immediate early genes of the AP-1 complex were not up-regulated. Our data show, 24 h after endotoxin stress, there is a regulation of a network of genes which represents a multifaceted preconditioning. As most important factors inhibition of apoptosis and antiproteatic mechanisms are identified. Heat-shock proteins seem to play no important role in the mechanism of endotoxin preconditioning.