The protective effect of ischemic preconditioning associated with altered gene expression profiles in rat lung after reperfusion.

BACKGROUND

Ischemia-reperfusion (IR) injury remains an important clinical problem after lung transplantation. It is well-known that ischemic preconditioning (IPC) markedly enhances the ability of organs to withstand a sustained ischemia and reperfusion injury. But the molecular mechanisms of this protective effect are poorly understood. Therefore, we used gene microarrays to profile gene expression patterns involved in ischemia precondition.

METHODS

Three groups of rats were studied: IR group (IR 0, 1, 3, 6, 24, n = 5 each group, IPC group (IP 1, IP 3, 6, 24 h, n = 5 each group) and Sham group (n = 5). Samples were collected from different groups. The RatRef-12 expression Beadchip (22,226 gene probes per array) was used to analyze the pattern of gene expression in all groups.

RESULTS

Microarray analysis showed that 648, 340, 711, 1279, and 641 genes were differentially expressed in IR 0-, 1-, 3-, 6- and 24-h groups, respectively. The profile revealed that IPC induced significant alterations of expression of many genes encoding inflammatory associated factors, oxidation and antioxidant molecules, apoptosis regulatory protein, metabolic enzyme, and ion channel protein.

CONCLUSIONS

The damage and repair after lung IR are a dynamic process. IPC affects gene expression profiles in IR lung tissue mainly within 6 h, and sustains until 24 h later. IPC reduces lung IR injury mainly through anti-inflammatory response, antioxidative stress, and regulating cell energy metabolism and ion channels.