Du Hongmei,Cai Weisong,Zeng Yuecan,Gao Song,Wu Rong.Pioglitazone ameliorating radiation fibrosis in rat hearts[J].Chinese Journal of Radiological Medicine and Protection,2015,35(12):891-896
Pioglitazone ameliorating radiation fibrosis in rat hearts
Received:June 04, 2015  
DOI:10.3760/cma.j.issn.0254-5098.2015.12.003
KeyWords:Pioglitazone  Radiation  Heart  Fibrosis  Transforming growth factor
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Author NameAffiliationE-mail
Du Hongmei Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China  
Cai Weisong Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China  
Zeng Yuecan Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China  
Gao Song Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China  
Wu Rong Department of Oncology, Shengjing Hospital of China Medical University, Shenyang 110004, China wur@sj-hospital.org 
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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.
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