Abstract: Objective   To detect the miRNA expression profiles of the donor heart after the heterotopic mouse-rat cardiac xenotransplantation and provide the experimental evidences for effective regulation of xenotransplantation rejection. Methods   The heterotopic cardiac mouse-rat xenotransplantation models were established by modified cuff sleeve method. The experimental animals were divided into syngeneic control group, xenogeneic group (24 hours) and xenogeneic group (arresting). Total of 579 miRNAs were detected by miRNA array and significantly differential expressed miRNAs in the cardiac xenotransplantation rejection were filtrated. MiR-146a and miR-451 in the three groups, which were obviously changed during xenotransplantation, were analysis by TaqMan? miRNA Assays, verifying the results of miRNA array. Results   There were 11 down-regulated miRNAs and 13 up-regulated miRNAs among the total 24 significantly differential expressed miRNAs found in xenogeneic (24hours) group comparing with control group. There were 12 down-regulated miRNAs and 13 up-regulated miRNAs among the total 25 significantly differential expressed miRNAs found in xenogeneic (arresting) group comparing with control group. MiR-146a and miR-451 in the three groups were obviously changed following xenotransplantation comparing with control group（respectively F =15.530,1.343, all P<0.05）and the results were accordant with the results of miRNA array. Conclusions   It is demonstrated that there are many significantly differential expressed miRNAs in xenotransplantation rejection. Simultaneous high expression of miR-146a and low expression of miR-451 in mouse-rat cardiac xenotransplantation rejection reveal the relevance to the regulation of immune response and inflammation. The miRNA is proposed to play an important role in regulating the cardiac xenotransplantation.

Key words: heart transplantation, transplantation, heterologous, microRNAs, microchip analytical procedures, gene expression profiling, allograft rejection