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硫化氢对大鼠心肌缺血/再灌注损伤的保护作用及其对c--Fos蛋白表达的影响

祝晓莹, 严晓红, 陈世健

武汉大学基础医学院生理系.湖北,武汉 430071

摘要

为探讨硫化氢(hydrogen sulfide, H_(2)S)对大鼠心肌缺血/再灌注(ischemia/reperfusion, I/R)损伤的保护作用及机制，雄性Sprague--Dawley大鼠被随机分为对照组(假手术组)、I/R组、2.8 #mu#mol/kg NaHS干预组、14 #mu#mol/kg NaHS干预组。结扎冠状动脉前降支30 min后，松扎再灌注60 min，心电图II导联检测和TTC染色测定心肌梗死面积评价制作的心肌I/R模型；测定血浆中H_(2)S浓度变化；监测血流动力学指标(LVSP, LV±dp/dt_(max))；HE染色和透射电镜观察心肌形态学改变；测定心肌组织中c--fos蛋白表达。结果显示：心肌I/R后血浆中H_(2)S浓度明显低于对照组[(30.32±5.26) vs (58.28±7.86) #mu#mol/L, {sl P}<0.05]；2.8和14 #mu#mol/kg NaHS均可显著改善I/R引起的心功能改变，且14 #mu#mol/kg NaHS的作用较2.8 #mu#mol/kg的强；14 #mu#mol/kg NaHS明显减轻心肌形态学及超微结构损伤，同时降低大鼠I/R心肌组织中c--fos蛋白表达(0.20±0.09 vs 0.32±0.15, {sl P}<0.01)。以上结果提示H_(2)S对大鼠心肌I/R损伤有保护作用，可能与其降低c--fos表达有关。

关键词： H_(2)S; 缺血/再灌注损伤; c-Fos蛋白; 心肌

H_(2)S protects myocardium against ischemia/reperfusion injury and its effect on c--Fos protein expression in rats

Zhu Xiaoying, Yan Xiaohong, Chen Shijian

Department of Physiology, School of Basic Medicine, Wuhan University.Wuhan 430071,Hubei

Abstract

The present study was aimed to study the effect of hydrogen sulfide (H_(2)S) on rat myocardial ischemia/reperfusion (I/R)injury and whether the effect is mediated by c-Fos protein expression. Male Sprague-Dawley rats were randomly divided into 4 groups:Control group: sham treatment; I/R group: the rat anterior descending branch of left coronary artery was occluded for 30 min and thenreleased to allow reperfusion for 60 min; Naris (exogenous H_(2)S donor) groups: the rats were pretreated with NaHs at 2.8 #mu#mol/kg bodyweight and 14 #mu#mol/kg body weight (i.v.), respectively, before I/R treatment. Hemodynamics (LVSP, LV±dp/dt_(max)) and electrocardio-gram (ECG, lead Ⅱ) were monitored continuously with multi-channel physiological signal analysis system after reperfusion. Myocar-dial infarct size was measured using triphenyltetrazolium chloride (TTC) staining. H_(2)S concentration in the plasma was determinedwith a spectrophotometer. Morphological and ultrastructural changes in myocardial tissue wereevaluated by HE staining and by atransmission electron microscope. The evaluation of c-Fos protein expression in myocardial tissue was performed by immunohistological staining. The results showed that H_(2)S concentration in rat plasma in I/R group was significantly decreased compared with that in thecontrol group [(30.32±5.26) vs (58.28±7.86) #mu#mol/L, P<0.05]. NaHs at 2.8 and 14 #mu#mol/kg body weight reduced the changes in LVSP,LV±dp/dt_(max) in rat myocardium induced by I/R injury. The values of LVSP, +dp/dt_(max) and -dp/dt_(max) at 60 min during myocardialreperfusion were enhanced from (75.93±1.10)%, (66.27±4.78)% and (66.01±4.79)% in I/R group to (84.34±2.24)%, (76.38±1.93)% and (75.47±5.29)% in 2.8 #mu#mol/kg body weight NaHs group (P<0.05, P<0.01, n=6), (88.40±2.88)%, (80.10±2.09)% and(80.48±6.20)% in 14 #mu#mol/kg body weight NaHS group (P<0.01, n=6), respectively. Compared with that in 2.8 #mu#mol/kg body weight NaHs group, the enhancing effect was more prominent in 14 #mu#mol/kg body weight NaHs group. NaHS at 14 #mu#mol/kg body weightmarkedly alleviated the injury in morphological changes and decreased c-Fos protein expression in myocardial tissue compared withthat in I/R group (0.20±0.06 vs 0.32±0.10, P<0.05). These results suggest that H_(2)S protects myocardium against I/R injury and thisprotective effect may be related to the down-regulation of c-Fos protein expression.

Key words: hydrogen sulfide;ischemia/reperfusion injury;c-Fos protein;myocardium

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引用本文：

祝晓莹, 严晓红, 陈世健. 硫化氢对大鼠心肌缺血/再灌注损伤的保护作用及其对c--Fos蛋白表达的影响[J]. 生理学报 2008; 60 (2): 221-227.

Zhu Xiaoying, Yan Xiaohong, Chen Shijian. H_(2)S protects myocardium against ischemia/reperfusion injury and its effect on c--Fos protein expression in rats. Acta Physiol Sin 2008; 60 (2): 221-227 (in Chinese with English abstract).