吡格列酮对大鼠心脏缺血再灌注损伤的保护作用  

Protective effects of pioglitazone on heart in ischemia-reperfusion injury rat

作　　者：曹泽玲[1] 叶平[1] 龙超良[2] 陈凯[2] 李小卫[2] 汪海[2] 

机构地区：[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

出　　处：《中国临床药理学与治疗学》2005年第10期1112-1117,共6页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家自然基金资助课题(№30270551)全军"十五"计划面上课题资助项目(№02M012)

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30min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2h组，再分为假手术组(n=5)、模型组(n=6)以及吡格列酮0．3mg·kg^(-1)(n=6)、1mg·kg^(-1)(n=7)和3mg·kg^(-1)(n=6)组，共5组，免疫组化检测MMP-2(matrix metalloproteinase-2)和PPARγ(peroxisome proliferator-activated receptoγ)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(necrosis，nec)与缺血区面积(area at risk，aar)之比减少28％(P＜0．01)，nec与左室面积(left ventricular，lv)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／dt_(max)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PPARγ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PPARγ而抑制MMP-2表达实现的。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 randomly divided into two groups. One was the group of 30 min reperfusion, which was subdivided into sham （n = 5）, model （vehicle, n = 6） and pioglitazone （3 mg·kg^-1, n = 7） with 30 min ischemia followed by 30 min 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 further subdivided into the sham （ n = 5）, model（vehicle, n = 6）, pioglitazone 0.3 mg·kg^-1 （ n = 6）, 1 mg·kg^-1 （ n = 7） and 3 mg·kg^-1 （ n = 5） group. Then immunohistochemistry and in situ hybridization were performed to detect the expression of MMP-2 and PPARγ protein and mRNA. 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/dtmax, as well as - dp/dtmax improved dramaticly at 1 rain and 30 min after reperfusion, respectively （P 〈 0.05）. In dose- dependent manner, the expression of MMP-2 protein and mRNA were depressed, while the PPARγ protein and mRNA were enhanced by pioglitazone. CONCLUSION： Pioglitazone has the protective ability against I/R injury evidenced by reducing area of MI and improving cardiac function. This may take place through the pathway in which PPARγ inhibiting MMP-2.

关 键 词：缺血再灌注 吡格列酮 MMP-2 心脏 PPARΓ 

分 类 号：R966[医药卫生—药理学]