Ischemic pre- and postconditioning has pronounced effects on gene expression profiles in the rat liver after ischemia/reperfusion.

Ischemic pre (IPC)- and postconditioning (IPO) protect the liver against ischemia/reperfusion injuries (IRI). Conditioning involves several different trigger factors, mediators, and effectors, many of which are affected during the early phase of reperfusion, ultimately resulting in decreased liver injuries. The aim of the present study was to investigate the genomic response induced by IPC and IPO in ischemia/reperfusion-damaged rat liver biopsies. Forty-eight male Wistar rats were divided into five groups: sham (n = 8), IRI (n = 10), IPC (n = 10), IPO (n = 10), and IPC + IPO (n = 10). The rat livers were subjected to 30 min of ischemia. Liver biopsies and blood samples were taken after 30 min of reperfusion. The biopsies were analyzed using cDNA microarrays with validation by quantitative RT-PCR. The significance analysis of microarray was used to identify genes with changed expression levels. A comparison analysis of the intervention groups showed a highly increased number of genes, with significantly different expression in the conditioned groups compared with the IRI group. A total of 172 genes were identified as the most highly affected, and these genes showed similar patterns with regard to the up- and downregulated expression levels within the conditioned groups. Pathway analysis of the 172 genes identified four networks that were involved in increased gene expression, cellular growth, and proliferation. In conclusion, the present study demonstrated that IPC, IPO, and IPC + IPO had pronounced effects on the expression levels of a large number of genes during early reperfusion. IPC, IPO, and IPC + IPO seem to mediate their protective effects by regulating the same genes and genetic networks. These identified networks are known to be involved in maintaining cellular homeostasis.

Expression of genes involved in rat liver angiogenesis after ischaemia and reperfusion: effects of ischaemic pre- and post-conditioning.

BACKGROUND: During surgery, ischaemic pre- (IPC) and post-conditioning (IPO) protects the liver against ischaemia/reperfusion injuries (I/R-injuries). The impact of ischaemic conditioning on liver regeneration has been less well studied. Angiogenesis is an important part of liver regeneration after hepatectomy. The aim of the present study was to investigate the effect of ischaemia/reperfusion and ischaemic conditioning on the expression of genes with angiogenic potential in a model of rat liver ischaemia. METHODS: A model of total liver ischaemia (30 min) and reperfusion (30 min) was employed using Wistar rats. Rats were randomized into five groups: (C) control (IRI) ischaemic, IPC, IPO and IPC + IPO. Liver enzymes were sampled at the end of reperfusion. Liver biopsies were analysed using cDNA microarrays. RESULTS: Alanine aminotransferase (ALT) increased significantly in all the ischaemic groups compared with controls (P= 0.000). Searching databases 99 genes involved in rat liver angiogenesis were identified. Compared with group (C) the number of genes significantly up-regulated was as follows: IRI (n= 5), IPC (n= 24), IPO (n= 33) and IPC + IPO (n= 18). No genes were down-regulated in the four groups compared with controls. CONCLUSION: Ischaemic conditioning, as demonstrated in the present study, seems to be potent activators of angiogenic genes. This might be favourable to the regenerating liver.