摘要
目的:研究环加氧酶2(COX-2)抑制剂尼美舒利和COX-1抑制剂比罗昔康在对抗心肌氧化应激损伤中的作用及其机制。方法:离体大鼠心脏行Langendorff灌流,分别给予H2O2、pyrogallol(可产生超氧阴离子)或VitC+Fe2+(可产生羟自由基),观察心脏收缩功能、心肌LDH和MDA含量。心肌COX的活性用PGI2的稳定产物6-Keto-PGF1α的含量表示。结果:尼美舒利(3mg/kg)可明显减轻H2O2引起的收缩功能下降(10min应激时LVDP为72%±10%vs61%±11%,P<0.05),减少LDH释放[(5.5±2.5)U/Lvs(8.0±2.1)U/L,P<0.05)]。而比罗昔康(3mg/kg)虽然能抑制H2O2应激时LVDP的下降(73%±10%vs61%±11%,P<0.05),却加重LVEDP的上抬[(29.00±5.61)mmHgvs(23.16±3.57)mmHg,P<0.01]。尼美舒利亦能减轻超氧阴离子和羟自由基引起的心肌损伤作用。尼美舒利和比罗昔康预处理对H2O2应激心肌6-Keto-PGF1α含量无明显影响。线粒体ATP敏感性钾通道(mitochondrial ATP sensitive potassium channel,mitoKATP)的阻断剂5-HD可取消尼美舒利减轻H2O2引起的LVDP和±dp/dtmax降低作用(分别为53%±12% vs 69%±3%、58%±11% vs 72%±7%和37%±8% vs 51%±4%,P<0.01)。结论:COX-2抑制剂尼美舒利可以对抗心肌氧化损伤,其机制通过非COX依赖性途径发挥作用,而mitoK可能参与尼美舒利的保护作用。
AIM： To investigate whether nimesulide [ a selective cyclooxygenase 2 （COX -2） inhibitor] and piroxicam （ an inhibitor of COX - 1 ） protect the rat hearts against oxidative stress induced by hydrogen peroxide, superoxide anion or hydroxyl free radical. METHODS： Cardiac contractility, lactate dehydrogenase （LDH） and malondialdehyde （MDA） were analyzed by the Langendorff method in isolated rat hearts. Production of 6 -Keto -PGF1α, a marker of COX activity, was measured in isolated rat hearts. RESULTS： Rat hearts were exposed to hydrogen peroxide （H2O2） , pyrogallol （which produced superoxide anion） or Vit C ＋ Fe^2＋ （which produced hydroxyl free radical） for 10 min followed by reperfusion for 30 min. H2O2 decreased cardiac contractility and increased LDH release, which was inhibited by nimesulide （3 mg/kg） [LVDP72% ±10% vs 61% ±11%, LDH （5.5 ±2.5）U/Lvs （8.0±2.1）U/L, P〈0.05]. Piroxicam （ 3 mg/kg） increased systolic function （ LVDP 73% ± 10% vs 61% ± 11% , P 〈 0. 05 ）, but exacerbated diastolic function [ LVEDP （29.00 ± 5.61 ） mmHg vs （23.16 ± 3.57） mmHg, P 〈 0. 01 ] in H2O2 treated rat hearts. Nimesulide also protected rat hearts against superoxide anion and hydroxyl free radical injury. Nimesulide and piroxicam had no effect on the content of 6 - Keto - PGF1α, in rat hearts. Mitochondrial ATP sensitive potassium channel （ mitoKATP ） inhibitor 5 - HD blocked the improvement of contractility （LVDP and ± dp/dtmax ） induced by nimesulide in H=O2 treated rat hearts （53% ± 12% vs 69% ± 3%, 58% ± 11% vs 72% ± 7% and 37% ± 8% vs 51% ± 4% respectively,P 〈 0. 01 ）. CONCLUSION ： The results suggests that COX -2 inhibitor nimesulide can protect rat hearts against oxidative injury. The protection is independent of COX activity. Activation of mitoKATP may be involved in nimsulide - induced cardioprotection in rat hearts.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2007年第12期2350-2356,共7页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No30400094)
关键词
氧化性应激
环加氧酶抑制药
钾通道
心脏
Oxidative stress
Cyclooxygenase inhibitors
Potassium channels
Heart
