Combined treatment with simvastatin and rapamycin attenuates cardiac allograft rejection through the regulation of T helper 17 and regulatory T cells.

Abstract

Allograft rejection is an important issue post cardiac transplantation. In order to investigate the effect of combined treatment with simvastatin and rapamycin on allograft rejection, a cardiac transplantation rat model was employed in the present study. The survival time of rats following cardiac transplantation was recorded, while histopathological alterations were assessed by hematoxylin and eosin staining. The levels of transcription factors were measured by reverse transcription-quantitative polymerase chain reaction. In addition, the levels of CD4+ interleukin (IL)-17+ cells and CD4+ forkhead box P3 (FOXP3)+ cells in the allografts and CD4+ T cells and CD8+ T cells in the spleens were detected by flow cytometry. The results of the current study demonstrated that, following treatment with simvastatin and rapamycin, the survival time of model rats was prolonged, and the histopathological damage was attenuated. Treatment with simvastatin and rapamycin also led to decreased retinoic acid receptor-related orphan receptor γt (RORγt) level, increased FOXP3 level, reduced levels of CD4+IL-17+, CD4+ T and CD8+ T cells, and increased level of CD4+FOXP3+ cells. In conclusion, the current study observed that simvastatin and rapamycin performed a synergistic effect to reduce cardiac transplantation rejection. Thus, combined therapy of simvastatin and rapamycin may be a promising adjuvant therapy to reduce rejection post cardiac transplantation.