| 杜红梅,蔡炜嵩,曾越灿,高嵩,吴荣.吡格列酮对大鼠放射性心肌纤维化的防治作用[J].中华放射医学与防护杂志,2015,35(12):891-896 |
| 吡格列酮对大鼠放射性心肌纤维化的防治作用 |
| Pioglitazone ameliorating radiation fibrosis in rat hearts |
| 投稿时间：2015-06-04 |
| DOI：10.3760/cma.j.issn.0254-5098.2015.12.003 |
| 中文关键词: 吡格列酮 照射 心脏 纤维化 转化生长因子 |
| 英文关键词:Pioglitazone Radiation Heart Fibrosis Transforming growth factor |
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| 中文摘要: |
| 目的 探究吡格列酮是否能减轻大鼠放射性心肌纤维化。方法 46只Sprague-Dawley(SD)大鼠按随机数字表法分成6组(对照组、吡格列酮10 mg ·kg-1 ·d-1组、吡格列酮20 mg ·kg-1 ·d-1组、18 Gy照射+安慰剂组、18 Gy照射+吡格列酮10 mg ·kg-1 ·d-1及18 Gy照射+吡格列酮20 mg ·kg-1 ·d-1组)。X射线局部照射大鼠心脏后,予以吡格列酮或者安慰剂1个月。3个月后,取心脏组织马松染色,观察心肌纤维化程度;Western blot分析各组蛋白表达程度;Real-time PCR观察各组过氧化物酶体增生物激活受体-γ(PPAR-γ)mRNA的表达。结果 马松染色示暴露于射线的大鼠心肌有明显纤维化,同时给予吡格列酮的大鼠心肌纤维化不明显。Western blot分析示PPAR-γ蛋白在照射组心脏的表达高于非照射组(F=12.435, P<0.05),照射+安慰剂组的转化生长因子-β1 (TGF-β1)蛋白表达高于其余5组(F=17.578,P<0.05),细胞周期蛋白依赖激酶5 (CDK5)蛋白在3个照射组的蛋白表达较高,但仅在照射+安慰剂组的升高差异有统计学意义(F=3.651,P<0.05)。Real-time PCR示PPAR-γ mRNA 在照射+吡格列酮20 mg ·kg-1 ·d-1组的表达高于吡格列酮20 mg ·kg-1 ·d-1组(F=2.333,P<0.05)。结论 吡格列酮通过其抗纤维化活性可减少大鼠放射性心肌纤维化,可能是通过抑制CDK5介导的PPAR-γ磷酸化而发挥作用。 |
| 英文摘要: |
| 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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