Aims: 

The aim of this study was to prove whether hypoxia inducible factor 1 alpha (HIF) gene therapy decreases oxidative stress in a model of intestinal ischemia in rats.

Methods: 

Male Wistar rats with a surgically induced ischemia of colon (caecum) or sham operated rats were treated by daily per os application of LB medium or E. coli with plasmids encoding listeriolysin and invasin (needed for the bactofection) and HIF. After one week, rats were sacrified, plasma and tissue samples were taken for analysis. Markers of oxidative stress – malondialdehyde, advanced oxidation protein products (AOPP) were measured. The expression of SOD1, SOD2 and VEGF was analyzed using real time PCR.

Results: 

No significant differences were found in the analysis of oxidative stress markers. A tendency to alleviate the tissue damage measured by AOPP was seen in HIF treated animals. Interestingly, all treatments reduced VEGF expression in comparison to ischemic group without treatment (p < 0.02). No significant differences were found in SOD1 and SOD2 expression, although the results for SOD2 indicated that HIF gene therapy might increase the antioxidant status. The differences were, however, marginally not significant.

Conclusion: 

Our results show some potential for bactofection mediated HIF gene therapy, but further studies are needed to improve the bacterial vector and, thus, the efficacy of gene transfer.