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

作　　者：杜红梅[1] 蔡炜嵩[1] 曾越灿[1] 高嵩[1] 吴荣[1] 

机构地区：[1]中国医科大学附属盛京医院肿瘤内科,沈阳110004

出　　处：《中华放射医学与防护杂志》2015年第12期891-896,共6页Chinese Journal of Radiological Medicine and Protection

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.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.

关 键 词：吡格列酮 照射 心脏 纤维化 转化生长因子 

分 类 号：R818[医药卫生—放射医学]