Pioglitazone ameliorating radiation fibrosis in rat hearts / 中华放射医学与防护杂志

ABSTRACT

Objective To explore whether pioglitazone can ameliorate radiation-induced fibrosis in rat heart.Methods A total of 46 Sprague-Dawley rats were divided into six groups (control group, pioglitazone (Pio) 10 mg·kg-1 ·d-1 group, Pio 20 mg·kg-1 ·d-1 group, 18 Gy irradiation + placebo group;18 Gy irradiation + Pio 10 mg·kg-1 ·d-1 , and 18 Gy irradiation + Pio 20 mg·kg-1 ·d-1 group).Experimental animals were exposed to radiation at the chest, then administered Pio or placebo for one month.At 3 months later, the rats were killed and their heart tissues were collected for Masson staining, Western blot analysis and real-time polymerase chain reaction assay (real-time PCR).Results Masson staining revealed significant myocardial fibrosis in rats exposed to radiation, while these changes were reduced when the rats were given Pio.Western blot analysis showed that the PPAR-γ protein expression in the heart tissue of irradiated rats were higher than in the non-irradiated group (F =12.435, P ＜ 0.05).Real-time PCR assay showed that PPAR-γ mRNA expression in the irradiation + Pio 20 mg· kg-1· d-1 group was higher than that in the Pio 20 mg· kg-1 ·d-1 group (F =2.333, P ＜ 0.05).The expression of TGF-β1 protein in the irradiation + placebo group were higher than those in the other five groups (F =17.578 ,P ＜0.05), and the CDK5 protein expression had a high level in the three irradiated groups while only the irradiation + placebo group was statistically higher than controls (F =3.651, P ＜ 0.05).Conclusions Pioglitazone may ameliorate radiation fibrosis in the rat heart through its anti-fibrotic activity, perhaps via inhibiting Cdk5-mediated PPAR-γ phosphorylation.