我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

二氮嗪预处理对大鼠离体缺血/再灌注心肌保护作用的研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2009年第2期
页码:
147
栏目:
基础研究
出版日期:
2009-03-30

文章信息/Info

Title:
Protective effect of diazoxide preconditioning on ischemia and reperfusion isolated working rat heart
作者:
韩劲松1; 阎德民2; 汪曾炜1; 朱洪玉1
1.沈阳军区总医院心血管外科，辽宁 沈阳 110016； 2.中国医科大学附属第一医院心脏外科，辽宁 沈阳 110001
Author(s):
HAN Jin-song1;  YAN De-min2;  WANG Zeng-wei1;  ZHU Hong-yu1
1.Department of Cardiovascular Surgery, General Hospital, Shenyang Military Area Command, Shenyang 110016, Liaoning, China; 2.Department of Cardiac Surgery, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, China
关键词:
二氮嗪预处理; 缺血再灌注; 过氧化物酶体增生激活受体γ协同刺激因子1α; 大鼠
Keywords:
diazoxide preconditioning;  ischemia/reperfusion;  PGC-1α;  rat
分类号:
R972.4
DOI:
-
文献标识码:
A
摘要:
目的 探讨二氮嗪预处理（DPC）对心肌缺血/再灌注损伤保护作用的机制。方法 Wistar大鼠26只,建立离体心脏Langendorff灌注模型，随机分成4组，即：①缺血/再灌注组（I/R组，n=10）：在心脏平衡灌流30 min后，缺血30 min再灌注K-H液1 h。②二氮嗪预处理组（DPC组,n=10）：在心脏平衡灌流10 min后，给予含二氮嗪（100μmol/L）的K-H液灌注5 min，再复灌不含二氮嗪的K-H液5 min后，给予含二氮嗪的K-H液灌注5 min；再复灌不含二氮嗪的K-H液5 min，然后缺血30 min，再灌注K-H液1 h。③空白对照组(n=3)：用等量盐水代替二氮嗪，过程同DPC组。④二甲基亚砜组（DMSO组，n=3）：用DMSO代替二氮嗪，过程同DPC组。取4组大鼠心尖肌制作冰冻切片和电镜标本。前者用于免疫组化染色检测过氧化物酶体增生激活受体γ协同刺激因子1α（PGC-1α）的表达；后者用于对心肌线粒体进行Flameng评分。结果 I/R组、DPC组、空白对照组和DMSO组的PGC-1α平均积分吸光度值（IODA），分别为（3.88±1.72）、（8.40±3.64）、（3.40±2.44）和（3.69±1.92），DPC组与其他组比较PGC-1α的表达明显增高（P<0.05）。Flameng评分：I/R组为（1.78±0.14），DPC组为（0.47±0.10），空白对照组为（1.69±0.23）、DMSO组为（1.72±0.17）,DPC组较其他组线粒体的损伤明显减轻（P<0.01）。结论 DPC后，心肌中PGC-1α的表达明显增加，线粒体的损伤明显减轻，提示DPC对心肌的保护作用与PGC-1α的高表达有关，PGC-1α可能是一种内源性心肌保护物质。
Abstract:
AIM To explore the mechanism of protection against myocardium ischemia/reperfusion (I/R) injury by diazoxide preconditioning (DPC). METHODS Isolated working heart models of Wistar rats were set up and were divided randomly into four groups. The I/R group (n=10): Equilibrium perfusion of 30 minutes was followed by a 60 minutes reperfusion. The DPC group (n=10) had a 10-min equilibration and two cycles of 5 min of 100 μm diazoxide perfusion followed by a 5-min diazoxide-free period before the 30 min ischemia and a 60-min reperfusion. The blank control group (n=3) and the dimethyl sulfoxide(DMSO) group (n=3) were perfused with the same treatment as in the DPC group, except that diazoxide was replaced with natriichloridum and DMSO. Frozen sections of myocardium at cardic apex were made and immunohistochemical staining was conducted to detect the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). 70 nm ultrathin sections were made and the mitochondria under each specimen was evaluated according to Flameng score. RESULTS The integrated optical density average (IODA) of PGC-1α expression was (8.40±3.64) in DPC group, (3.88±1.72) in I/R group,（3.40±2.44）in blank control and （3.69±1.92） in DMSO group. The expression of PGC-1α in DPC group was significantly higher than that in other groups（P<0.05）. Flameng score of was（1.78±0.14） in I/R group, （0.47±0.10） in DPC group, (1.69±0.23) in blank control and (1.72±0.17) in DMSO group, with significant difference between DPC group and other groups (P<0.01). CONCLUSION DPC can protect cardiomyocytes from ischemia and reperfusion injury, which may be related to the high expression of PGC-1α. PGC-1α may be an endogenous defense substance of myocardium.

参考文献/References

[1］ Ardehali H, O’Rourke B. Mitochondrial K(ATP) channels in cell survival and death ［J］. J Mol Cell Cardiol, 2005, 39(1):7-16.

［2］ Flameng W, Borgers M, Daenen W, et al. Ultrastructual and cytochemical correlates of myocardial protection by cardiac hypothermia in man ［J］. J Thorac Cardiovasc Surg, 1980, 79(3):413-424.

［3］ Garlid KD, Paucek P, Yarov-Yarovoy V, et al. Cardioprotective effect of diazoxide and its interaction with mitochondrial ATP-sensitive K+ channels［J］. Circ Res, 1997, 81(6):1072-1082.

［4］ Garlid KD. Opening mitochondrial K (ATP) in the heart-what happens, and what does not happen［J］. Basic Res Cardiol, 2000, 95(4):275-279.

［5］Puigserver P, Spiegelman BM. Peroxisome proliferator-activated receptor-gamma coactivator 1alpha (PGC-1alpha): transcriptional coactivator and metabolic regulator［J］. Endocrine Rev, 2003, 24(1):78-90.

［6］ Kelly DP, Scarpulla RC. Transcriptional regulatory circus controlling mitochondrial biogenesis and function［J］. Genes Dev, 2004, 18(4):357-368.

［7］ Van den Bosch BJ, van den Burg CM, Schoonderwoerd K, et al. Reginal absence of mitochondria causing energy depletion in the myocardium of muscle LIM protein knockout mice［J］. Cardiovasc Res, 2005, 65(2):411-418.

［8］ Vimaleswaran KS, Radha V, Ghosh S, et al. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians［J］. Diabetic Med, 2005, 22(1):1516-1521.

［9］ Yoon JC, Puigserver P, Chen G, et al. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1［J］. Nature, 2001, 413(6852):131-138.

［10］周逸，唐其柱. ATP敏感性钾通道在缺血预适应中的作用［J］. 心脏杂志， 2005， 17(1): 83-86.

备注/Memo

备注/Memo:
收稿日期：2007-7-16.基金项目：辽宁省教育厅高等学校科学研究项目资助（05L467） 作者简介：韩劲松，主治医师，硕士Email:hanjs0216@sina.com
更新日期/Last Update: 2009-04-16