放射性心脏损伤模型大鼠接受吡格列酮干预的心脏保护作用  

Protective effect of pioglitazone in rat models of radiation-induced heart injury

作　　者：宋扬[1] 吴荣[1] 曾越灿[1] 张振勇[1] 杜红梅[1] 

机构地区：[1]中国医科大学附属盛京医院第二肿瘤病房,辽宁省沈阳市110022

出　　处：《中国组织工程研究》2015年第5期674-680,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金项目(81201803)~~

摘　　要：背景:激活过氧化物酶体增殖物活化受体γ信号途径在心血管系统有许多正效应。血管紧张素Ⅱ与心肌的纤维化密切相关,然而却很少有研究关注激活过氧化物酶体增殖物活化受体γ途径能否通过减弱血管紧张素Ⅱ的表达从而改善放射性心肌损伤。目的:探索激活过氧化物酶体增殖物活化受体γ后血管紧张素Ⅱ1型受体对放射性心脏损伤模型大鼠的作用。方法:60只大鼠随机等分为对照组、吡格列酮组、模型组及照射+低、高剂量吡格列酮组。模型组及照射+低、高剂量吡格列酮组大鼠采用前后对穿照射方法接受6 MV高能X射线照射野心前1.5 cm×1.5 cm,照射剂量300 c Gy/min。照射完后6 h时,低、高剂量吡格列酮组大鼠分别接受10,20 mg/kg吡格列酮灌胃,此后每天灌胃1次,连续灌胃30 d;模型组大鼠灌胃2 m L蒸馏水。吡格列酮组大鼠在对应时间灌胃10 mg/kg吡格列酮。结果与结论:给予吡格列酮干预后,受照射大鼠的心脏组织损伤减轻,心脏纤维化减轻,心脏组织中血管紧张素Ⅱ1型受体蛋白及m RNA表达水平减少。提示吡格列酮干预可降低血管紧张素Ⅱ1型受体在大鼠放射性心脏损伤中的表达,提示激活过氧化物酶体增殖物活化受体γ途径可能对放射性心脏损伤有保护作用。BACKGROUND：There are many positive effects by activation of peroxisome proliferator activated receptor-gamma （PPARγ） signal pathway in cardiovascular system. Angiotensin II is closely related with myocardial fibrosis, however, there are few articles demonstrating that the activation of PPARγsignal pathway can weaken the expression of angiotensin II to improve the radiation-induced heart injury. OBJECTIVE：To evaluate the effect of angiotensin II type 1 receptor in the rat model of radiation-induced heart injury after PPARγsignal pathway is activated. METHODS：Sixty rats were randomly and equal y divided into five groups：control, pioglitazone, model, radiation＋low-dose pioglitazone, radiation＋high-dose pioglitazone. In the model, radiation＋low-dose pioglitazone, radiation＋high-dose pioglitazone groups, rats received 6 MV high energy X-ray irradiation at the range of 1.5 cm × 1.5 cm and the irradiation dose of 300 cGy/min, for 6 hours. Furthermore, rats in the radiation＋low-dose pioglitazone and radiation＋high-dose pioglitazone groups were given 10 and 20 mg/kg pioglitazone by lavage, for 30 days;rats in the model group were given 2 mL distil ed water. In the pioglitazone group, rats were treated with 10 mg/kg pioglitazone by lavage. RESULTS AND CONCLUSION：After rats were treated with pioglitazone, the heart injury and the heart fibrosis in the irradiated rats were decreased. The expressions of angiotensin II type 1 receptor mRNA and protein in the heart tissue were down-regulated. Experimental findings indicate that, pioglitazone intervention downregulates the expression of angiotensin II type 1 receptor in the rat models of radiation-induced heart injury and activation of PPARγsignal pathway al eviates the radiation-induced heart injury.

关 键 词：实验动物 心脏及血管损伤动物模型 放射治疗 放射性心肌损伤 过氧化物酶体增殖物活化受体Γ 过氧化物酶体增殖物活化受体γ激动剂 吡格列酮 血管紧张素Ⅱ 血管紧张素Ⅱ1型受体 国家自然科学基金 

分 类 号：R318[医药卫生—生物医学工程]