吡格列酮对大鼠心脏缺血再灌注损伤的保护作用

中国临床药理学与治疗学 ›› 2005, Vol. 10 ›› Issue (10): 1112-1117.

吡格列酮对大鼠心脏缺血再灌注损伤的保护作用

曹泽玲^1,2, 叶平¹, 龙超良², 陈凯², 李小卫², 汪海²

¹解放军总医院老年心血管二科, 北京 100853;
²军事医学科学院药物毒物研究所, 北京 100850

收稿日期:2005-04-14 修回日期:2005-07-08 发布日期:2020-11-23
通讯作者: 叶平,女,医学博士,教授,主任医师,博士生导师,研究方向:脂质代谢和动脉粥样硬化的基础和临床。Tel:010-66437912E-nail:yeping@sina.com
作者简介:曹泽玲,女,在读博士,研究方向。
基金资助:
国家自然基金资助课题(No30270551);全军“十五”计划面上课题资助项目(No02M012)

Protective effects of pioglitazone on heart in ischemia-reperfusion injuryrat

CAO Ze-ling^1,2, YE Ping¹, LONG Chao-ling², CHEN Kai², LI Xiao-wei², WANG Hai²

¹Department of Geriatric Cardiology, General Hospital Of PLA, Bejing 100850, China;
²Department of Cardioascular Pharmacology, Beljing Institute of Pharmacology and Toxicology Beying 100850, China

Received:2005-04-14 Revised:2005-07-08 Published:2020-11-23

摘要/Abstract

摘要： 目的: 观察吡格列酮对大鼠在体心肌缺血再灌注损伤的影响,并探讨其发生机制。方法: 将实验动物随机分为两组,一为再灌注30 min组,进一步分为假手术组(n = 5)、模型组(n = 6) 和吡格列酮(3mg·kg^-1, n=7)组,测定有关心功能指标和心肌梗死面积;另一为再灌注2 h组,再分为假手术组(n = 5)、模型组(n = 6)以及吡格列酮0.3 mg·kg^-1(n = 6)、1 mg·kg^-1(n = 7)和3 mg·kg^-1 (n = 6)组,共5组,免疫组化检测MMP-2(matrix metallopro-teinase-2)和PPARY (peroxisome proliferator activatedrecepton'Y)蛋白质表达,原位杂交方法检测其mRNA表达,结果:与模型组比较,吡格列酮组梗死面积(necronis,nec)与缺血n区而积(area at risk, aar)之比减少28% (P< 0.01),ne与左室面积(left ventricular,Iv)之比减少32% (P < 0.01);吡格列酮作用后心率和反映心脏收缩功能指标的+ dp/dtm以及反映舒张功能指标的-dp/dt_max明显改善(P<0.05~0.001),吡格列酮0.3、1、3 mg·kg^-1可呈剂量依赖性减少MMP-2蛋白质和mRNA表达,增加PPARY蛋白质和mRNA表达(P < 0.05)。结论: 吡格列酮对心肌缺血再灌注损伤有保护作用,且这种保护作用可能是通过激活PPARY而抑制MMP-2 表达实现的。

关键词: 缺血再灌注, 吡格列酮, MMP-2, 心脏, PPARY

Abstract: AIM: To observe the effects of pioglitazone on the hearts of the rat's models of ischemia-reperfusion in vivo.METHODS: Sprague-dawley rats were randonnly divided into two groups. One was the group of 30 min reperfusion, which was subdivided into sham (n=5), model (veahic, n=6) and pioglitzone (3mg·kg^-1, n = 7) with 30 min ischemia followed by 30min reperfusion to detect some data related to cardiac function and the area of myocardium infarction (MI). Another was the group of 2 h reperfusion, which was fur-ther subdivided into the sham (n = 5), model (venicle,n = 6), pioglitazone 0.3 mg·kg^-1 (n = 6), 1 mg·kg^-1 (n = 7) and 3 mg·kg^-1. (n = 5). Then Immunohistochemistry and in situ hybridization were performed todetect the express of MMP-2 and PPARTY and RNA.RESULTS: Compared with the model group nec/aar after injecting pioglitazone decreased by 28% (P< 0.01). The ratio of nec/lv reduced to 32% (P <0.01). Heart rate, + dp/dt_max, as well as-dp/dt_max improved dramatiely at 1 min and 30 min after reperfusion, respectively (P 0.05). In dose-dependent manner,the expression of MMP-2 protein and MRNA were de-resseed, while the PPARY protein and MRNA were en-hanced by pioglitazone.CONCLUSION: Pioglitazonehas the protective ability against I/R injury evidenced byreducing area of MI and improving cardiac function. Thismay take place through the pathway in which PPARY inhibiting MMP-2.

Key words: ischemareperfusion, pioglitazone, ap-optosis, heart, PPARY

中图分类号:

H966

曹泽玲, 叶平, 龙超良, 陈凯, 李小卫, 汪海. 吡格列酮对大鼠心脏缺血再灌注损伤的保护作用[J]. 中国临床药理学与治疗学, 2005, 10(10): 1112-1117.

CAO Ze-ling, YE Ping, LONG Chao-ling, CHEN Kai, LI Xiao-wei, WANG Hai. Protective effects of pioglitazone on heart in ischemia-reperfusion injuryrat[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(10): 1112-1117.

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