哌芳安他对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 (6): 604-612.

哌芳安他对心脏缺血再灌注损伤的保护作用

曹泽玲^1,2, 陈凯¹, 杨庭树³, 龙超良¹, 李小卫¹, 叶平², 汪海¹

¹军事医学科学院毒物药物研究所, 北京100850;
²解放军总医院老年心血管科,
³心内科, 北京100853

收稿日期:2004-12-20 修回日期:2005-03-06 出版日期:2005-06-26 发布日期:2020-11-12
通讯作者: 汪海, 男, 医学博士, 研究员, 博士生导师, 研究方向:心血管药理和新药研究。Tel:010-66932651 E-mail: wh@nic.bmi.ac.cn.
作者简介:曹泽玲, 女, 在读博士, 研究方向:冠心病防治。
基金资助:
军队医药卫生“十五” 重点课题(NO0Z025)

Protective effects of pivanampeta on ischemia-reperfusion injury of rat heart

CAO Ze-ling^1,2, CHEN Kai¹, YANG Ting-shu³, LONG Chao-liang¹, LI Xiao-wei¹, WANG Hai¹

¹Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;
²Department of Geriatric Cardiology,
³Department of Cardiology, General Hospital of PLA, Beijing 100853, China

Received:2004-12-20 Revised:2005-03-06 Online:2005-06-26 Published:2020-11-12

摘要/Abstract

摘要： 目的: 观察哌芳安他(pivanampeta, Piv) 对大鼠在体心肌缺血再灌注损伤的影响。方法: 实验动物分为2 组, 一组为缺血30 min 再灌注30 min 组, 再分为假手术组、对照组和Piv 9 mg·kg-1用药组, 测定有关心功能指标和心肌梗死面积;另一组为缺血30 min 再灌注2 h 组, 再分为假手术组、模型组以及Piv 3、6 和9 mg·kg^-1 用药组, 各用药组于缺血前30 min 静脉注射给药, 再灌注2 h 后取心脏标本石蜡包埋后切片, 免疫组化法检测Bax 、Bcl-2 、caspase-3、MMP-2、和PPARγ蛋白质表达, 原位杂交方法检测MMP-2 和PPAR γmRNA 表达, TUNEL 法和DNA 凝胶电泳观察心肌细胞凋亡。结果: (1) 与对照组比较,Piv 3 mg·kg^-1组坏死面积(nec) 与缺血面积(aar) 之比减少21 %(P <0.01), 坏死面积与左室面积(lv) 之比减少22 %(P <0.01) 。心率、反映心脏收缩功能的指标+ dp /dt_max 和V_max 以及反映心脏舒张功能的指标-dp /dt_max 分别在再灌注1 min 和30 min 明显改善(P <0.05) 。(2) TUNEL 法检测, Piv 各亚组降低细胞凋亡作用显著(P <0.05), 但DNA 凝胶电泳检测, 模型组、Piv 3 、6 mg·kg^-1组可见到DNA 梯带,假手术组和Piv 9 mg·kg^-1组则无。(3) 免疫组化检查, Piv 3 、6 和9 mg·kg^-1 呈剂量依赖性减少Bax 、caspase-3 、MMP-2 蛋白质和MMP-2 的mRNA 表达, 增加Bcl-2 、PPARγ (peroxisome proliferator-activatedreceptorγ) 蛋白质和PPARγmRNA 表达。结论: Piv 预处理对心肌缺血再灌注损伤有保护作用, 表现为减少心肌梗死面积、改善心功能、减少心肌细胞凋亡。

关键词: 缺血再灌注, 哌芳安他, 细胞凋亡, 心脏, PPARγ

Abstract: AIM: To observe the effects of pivanampeta (Piv) on ischemia-reperfusion injury of rat heart in vivo. METHEDS: Sprague-Dawley rats were randomly divided into two groups. One was 30 min reperfusion group, which was subdivided into sham, control and Piv groups with 30 min ischemia followed by 30 min reperfusion to detect some data related to cardiac function and the area of myocardium infarction. Anotherwas 2 h reperfusion group, which was further subdivided into such sections as follows: sham, model, Piv 3, 6 and 9 mg·kg^-1 groups.Apart from the sham, Piv and NS (control) groups were administered intravenously 30 min before occlusion. Then hearts were excised, paraffined and cut into 4 μm think. Immunohistochemistry, in situ hybridization, TUNEL and DNA agarose gel electrophoresis were performed to detect the expression of Bax, Bcl-2, caspase-3, MMP-2 and PPAR γprotein and MMP-2, and PPARγmRNA. RESULTS: Compared with control group, the ratio of nec aar after Piv injected decreased 21 % (P <0.05), while nec lv reduced to 22 %(P < 0.05). Heart rate, +dp /dt_max and V_max representing the systolic function of heart as well as-dp /dt_maxwhich was the indicator of diastole improved dramaticly at 1 min and 30 min after reperfusion, respectively (P <0.05). In dose-dependent manner, the expression of Bax and caspase-3 protein, MMP-2 protein and mRNA depressed, while the PPARγprotein and mRNA enhanced by Piv. The apoptotic index of subgroups injected Piv reduced with important significance by TUNEL compared with model(P <0.05). DNA ladder existed in model, Piv 3、6 mg·kg^-1, rather than Piv 9 mg ·kg^-1 by agarose gel electrophoresis. CONCLUSION: Piv shows the protective ability against I R injury of myocardium. Piv administration may reduce the area of MI and improve cardiac function as well as decrease apoptotic cardiomyocytes.

Key words: ischemia-reperfusion, pivanampeta, cell apoptosis, heart, PPARγ

中图分类号:

R966

曹泽玲, 陈凯, 杨庭树, 龙超良, 李小卫, 叶平, 汪海. 哌芳安他对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(6): 604-612.

CAO Ze-ling, CHEN Kai, YANG Ting-shu, LONG Chao-liang, LI Xiao-wei, WANG Hai. Protective effects of pivanampeta on ischemia-reperfusion injury of rat heart[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2005, 10(6): 604-612.

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