Up-regulation of peroxisome proliferator-activated receptor gamma in radiation-induced heart injury in rats

Abstract

To explore the expression level and the role of peroxisome proliferator-activated receptor gamma (PPAR-γ) in radiation-induced heart injury in a rat model, thirty-two Sprague-Dawley rats were divided into three groups (the control group, the 15-Gy irradiation group and the 18-Gy irradiation group). Experimental animals were exposed to radiation generated by a linear accelerator at the chest and killed after 3months. Heart tissues from these animals were removed for Masson staining, PPAR-γ immunohistochemical staining, Western blot analysis and real-time polymerase chain reaction assay (RT-PCR). In addition, the protein expression of matrix metalloprotein-1 (MMP-1), tissue inhibitor of metalloproteinase-1 (TIMP-1) and transforming growth factor type beta1 (TGF-β1), all of which are associated with fibrosis, was measured. Masson staining revealed significant myocardial fibrosis, degeneration and necrosis in rats exposed to radiation. The results of immunohistochemical staining and Western blot analysis showed that PPAR-γ protein expression in hearts of the irradiation groups was significantly higher than in the control group, especially in myocardium and vascular endothelial (p<0.05). RT-PCR results also showed a parallel increase in PPAR-γ mRNA expression in the heart of the irradiation groups compared with the control group (p<0.05). The expression of MMP-1 protein was not significantly different in three groups (p>0.05). The expression of TIMP-1 and TGF-β1 proteins was, however, higher in two irradiation groups than in the control group (p<0.05). These data demonstrate that PPAR-γ expression is up-regulated on both mRNA and protein levels in heart injured by radiation. PPAR-γ may play an important role in radiation-induced heart injury.