吡格列酮在大鼠放射性肺纤维化中保护作用的研究  

Protective effects of pioglitazone on radiation induced lung fibrosis

作　　者：吴荣[1] 孙宇楠[1] 张振勇[1] 曾越灿[1] 曹硕[1] 

机构地区：[1]中国医科大学附属盛京医院肿瘤科,沈阳110022

出　　处：《实用药物与临床》2015年第1期13-17,共5页Practical Pharmacy and Clinical Remedies

基　　金：国家自然科学基金资助项目(81201803)

摘　　要：目的探讨吡格列酮在放射性肺纤维化中的保护作用,以及对AT1R(血管紧张素Ⅱ1型受体表达的影响。方法 SD大鼠60只,共分为5组。空白组:不接受任何干预;照射+安慰剂组:接受12 Gy照射+安慰剂干预;单独给药组:接受吡格列酮10 mg/(kg·d)干预;照射+吡格列酮a组:接受12 Gy照射+吡格列酮10 mg/(kg·d)干预;照射+吡格列酮b组:接受12 Gy照射+吡格列酮20 mg/(kg·d)干预。采用HE及M asson染色观察大鼠肺组织纤维化情况;采用免疫组化观察AT1R在肺组织中的分布情况;采用蛋白免疫印迹杂交及RT-PCR检测AT1R蛋白及mRNA的表达情况。结果 HE及M asson染色显示,受照射大鼠肺组织细胞出现变性、坏死,肺组织出现明显纤维化;大鼠给予吡格列酮干预后,受照射大鼠的肺组织损伤减轻,肺组织纤维化减轻;免疫组化提示,照射后大鼠肺组织及上皮细胞中AT1R表达较空白组及单独给药组明显,照射+吡格列酮组的AT1R表达较照射+安慰剂组少;Western blot及RT-PCR提示,接受吡格列酮干预的受照射大鼠,AT1R蛋白及mRNA表达水平被明显抑制。结论吡格列酮在放射性肺纤维化中具有保护作用,其可能通过下调AT1的表达来实现对放射性肺损伤的保护作用。Objective To investigate the protective effects of pioglitazone on radiation induced lung fibrosis,and the effects on the expression of AT1 receptor. Methods Sixty SD rats were divided into 5 groups. The blank group： without any intervention. The irradiation plus placebo group： receiving 12 Gy irradiation plus placebo intervention. The single drug group： receiving only 10 mg /（ kg·d） pioglitazone intervention. The irradiation plus pioglitazone a group： receiving 12 Gy irradiation plus 10 mg /（ kg·d） pioglitazone intervention. The irradiation plus pioglitazone b group： receiving 12 Gy irradiation plus 20 mg /（ kg·d） pioglitazone intervention. HE and Masson staining were used to observe the lung tissue injury. The distributions of AT1R in lung tissue were observed by immunohistochemistry. The expression of AT1R protein and mRNA were detected by Western blot and RT-PCR. Results HE and Masson staining indicated that the lung tissue of irradiation rats showed degeneration and necrosis,the lung tissue appeared obvious fibrosis. When the rats were treated with pioglitazone after irradiation,the lung injury and fibrosis decreased. The immunohistochemical staining showed that after irradiation,the expressions of AT1R of lung tissue was more obvious than those of blank group and the single drug group. The expressions of AT1R of irradiation plus pioglitazone group was less obvious than that of irradiation plus placebo group. The Western blot and RT-PCR indicated that after the pioglitazone intervention,the expressions of AT1 protein and mRNA of irradiation rats were significantly inhibited. Conclusion Pioglitazone has protective effects on radiation induced lung fibrosis,possibly through the down-regulation of the expression of AT1R.

关 键 词：放射性肺纤维化 吡格列酮 血管紧张素Ⅱ1型受体 过氧化物酶体增殖物激活受体Γ 

分 类 号：R730.55[医药卫生—肿瘤]