Changes of autophagy level after cardiac transplantation in mice and its physiological significance

Objective To investigate the change of autophagy level after cardiac ransplantation in mice and its relationship with immune exclusion. Methods BALB/c was used as donor, C57BL/6 as receptor and Cuff vascular anastomosis to carry out heterotopic heart transplantation in the neck of mice. At 4 and 8 days after transplantation, autophagy related gene p62 was analyzed by Western blot to detect the changes of autophagy in the heart of transplanted mice; enzyme linked immunosorbent assay (ELISA) was used to analyze the expression level of interferon (IFN)-γ and interleukin (IL)-17. After the treatment of rapamycin, the autophagy level, the survival time and the cytokine level were analyzed in the control group and the experimental group. Results Compared with the normal donor heart (1.23± 0.31), the level of autophagic protein p62 (0.43±0.18) of donor heart after fourth days in transplantation significantly reduced (t=2.198, P=0.010), and the p62 level of autophagic protein (1.19 ±0.29) after fourth days in transplantation was not statistically significant (t=0.194, P=0.291). Compared with IFN-γ and IL-17 in normal mice, IFN-γ and IL-17 in the recipient mice significantly reduced in fourth days after transplantation (t=3.127, P=0.000; t=4.015, P=0.000). The level of IFN-γ and IL-17 in the sera of the recipient mice eighth days after transplantation significantly enhanced than that of IFN-γ and IL-17 in normal mice (t=4.192, P=0.000; t=5.091, P=0.000). The p62 level of donor heart was significantly lower than that of the control group after treatment (t=5.921, P=0.000, t=6.994, P=0.000). The survival time of the heart in the experimental group after treatment (11.5 days) was significantly longer than that of the control group (LogRank=3.129, P=0.010). The level of IFN-γ and IL-17 in the serum of the experimental group fourth and eighth days after transplantation was significantly lower than that of the control group (t=5.109, P=0.000; t=5.409, P=0.000 and t=7.098, P=0.000; t=6.153, P=0.000). Conclusion Autophagy can reduce immune rejection in cardiac allograft mice and improve the survival of transplanted heart. Key words: Heart transplantation; Autophagy; Immune rejection