曲美他嗪与帕瑞昔布钠联合给药对急性心肌梗死期大鼠心脏的保护作用
摘要
目的:
通过结扎大鼠冠状动脉左前降支(Left Anterior Descending, LAD)造成大鼠急性心肌缺血模型,观察缺血大鼠心肌组织中COX-2表达变化情况。通过给予选择性COX-2抑制剂帕瑞昔布,初步探讨COX-2在急性心肌缺血大鼠心肌组织中所发挥的作用。
方法:
一、为观察COX-2在急性心肌梗死大鼠心肌组织中表达的变化以及发挥的作用,分别取造模成功第2天至第7天的大鼠。测定心功能后迅速处死,取心肌组织,分别检测COX-2蛋白表达,梗死面积,细胞凋亡率。
二、为观察帕瑞昔布钠对心肌的保护作用,大鼠被分为:1、假手术组(Sham):只穿线,不结扎;2、模型组(AMI):AMI+生理盐水腹腔注射或生理盐水灌胃;3、帕瑞昔布钠低剂量组:AMI+Parecoxib (ip.0.2 mg/kg/d);4、帕瑞昔布钠中剂量组:AMI+Parecoxib (ip.0.4 mg/kg/d);5、帕瑞昔布钠高剂量组:AMI+Parecoxib (ip.0.8 mg/kg/d)。从造模第3日至第7日给药,术后第8天检测大鼠心功能(LVSP、LVEDP、+dp/dtmax、-dp/dtmax),测定心脏梗死面积, Bax和Bcl-2基因表达, COX-2、Bax、Bcl-2的蛋白表达,Caspase-3活化以及心肌梗死周边区细胞凋亡率。以观察给予帕瑞昔布钠治疗后,大鼠心肌组织损伤的变化情况。
结果:
1. COX-2蛋白在Sham组大鼠心肌组织中几乎不表达。与Sham组相比,大鼠冠脉左前降支结扎后心肌梗死周边区COX-2蛋白表达升高(P<0.01);随着梗死天数的增加,COX-2蛋白表达逐渐增高,并于第3日达到峰值,此后梗死心肌COX-2蛋白含量稳定于此浓度。
2.帕瑞昔布钠浓度梯度给药后,心梗大鼠心肌细胞中的COX-2表达下降(P<0.05),随着给药浓度的增加,COX-2蛋白表达逐渐下降,说明帕瑞昔布钠能够减少心梗大鼠心肌细胞中COX-2的蛋白表达。
3.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,受到损伤的心肌收缩功能(LVSP、+dp/dtmax)明显恢复,差异具有著性意义(P<0.05);心肌舒张功能(LVEDP、-dp/dtmax)虽有上升趋势,但是差异无显著性意义(P>0.05),且这种改变具有一定的浓度依赖性。
4.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,各组大鼠梗死面积有改变,但是差异不具有显著性意义(P>0.05)。
5.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,大鼠梗死周边区细胞的DNA Ladder条带化程度减弱,且随着给药浓度的增加,心肌细胞Ladder条带化程度持续减弱。
6.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,心梗周边区caspase-3的活化程度下降(P<0.05),且随着给药浓度的增加,caspase-3活化程度减弱,差异具有统计学意义(P<0.05)。
7.与AMI组相比,梯度浓度给予帕瑞昔布钠治疗后,Bax/Bcl-2的mRNA和蛋白表达比例均下降(P<0.05);随着给药浓度的增加,Bax/Bcl-2的mRNA和蛋白表达比例逐渐下降(P<0.05)。
结论:
心肌急性缺血过程中,心肌细胞中COX-2的基因水平和蛋白水平均增高。帕瑞昔布钠可以浓度依赖性保护心肌细胞免受心肌缺血缺氧的损伤。其保护急性心肌缺血大鼠心肌细胞的机制可能与抑制缺血组织细胞凋亡有关。
目的:
通过在急性心肌缺血模型中给予抗代谢药曲美他嗪与选择性COX-2抑制剂帕瑞昔布钠,观察他们是否具有协同保护急性心肌梗死大鼠心脏的作用。
方法:
80只雄性SD大鼠随机分为1、假手术组(Sham):只穿线,不结扎;2、模型组(AMI):AMI+生理盐水腹腔注射或生理盐水灌胃;3、曲美他嗪给药组:AMI+TMZ(ig. 20 mg/kg/d);4、帕瑞昔布钠给药组:AMI+Parecoxib (ip. 0.75 mg/kg/d);5、曲美他嗪和帕瑞昔布钠联合给药组:AMI+ TMZ(ig. 20 mg/kg/d)+Parecoxib (ip. 0.8 mg/kg/d)。大鼠实施冠状动脉左前降支结扎后,第3d开始给药,第8d检测大鼠心功能(HR、LVSP、LVEDP、+dp/dtmax、-dp/dtmax),测定心脏梗死面积, Bax和Bcl-2基因表达, COX-2、Bax、Bcl-2的蛋白表达,Caspase-3活化率以及心肌梗死周边区细胞凋亡率。
结果:
1.与假手术组相比,AMI模型组大鼠心肌梗死周边区COX-2蛋白表达明显增高(P<0.01);帕瑞昔布钠治疗组与AMI模型组相比,COX-2表达下降(P<0.01);
2.联合给药治疗组与模型组相比,能显著改善心肌梗死大鼠的心脏收缩功能(LVSP与+dp/dtmax)(P<0.05),并减小心肌梗死面积(P<0.05),心肌梗死周边区细胞的凋亡程度下降。并且联合给药治疗效果优于单独给药。
3.联合给药治疗组与模型组相比,Bax/Bcl-2 mRNA和蛋白表达比例显著降低(P<0.05),Caspase-3活性率下降(P<0.05)。
结论:
帕瑞昔布钠与曲美他嗪联合给药具有一定的协同保护缺血心肌的作用,其机制可能与共同抑制心肌细胞凋亡有关。
Objective:
Cyclo-oxygenase-2 (COX-2) is the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin. A great interest in COX-2 has developed over the years because it`s only induced in cardiomyocytes in response to stress, such as ischaemia and endotoxin, While not present in most normal cells. The ligation of the left coronary artery was performed to detected COX-2 protein levels in the myocardium in the ischemic border zone of the rat heart. Then, a selected COX-2 inhibitor Parecoxib sodium was applied to survey the the effects of COX-2 in ischemia myocardium in AMI rats.
METHODS :
1. All rats were sacrificed after the ligation of the left coronary artery was performed for two to seven days. The heart function was detected by Pc-lab bioinstruments. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
2. To observe the protective effects of parecoxib sodium, ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 5 groups: 1. Sham group; 2. AMI group: AMI+physiological saline; 3. Low dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.2 mg/kg/d); 4. Moderate dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.4 mg/kg/d); 5. High dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.8 mg/kg/d). The heart function was detected by Pc-lab bioinstruments. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
RESULTS:
1. COX-2 protein wan not expression in Sham group. Compared with Sham group , AMI group showed increased expression of COX-2 protein (P<0.01). It rose up gradually and the peak concentration appeared on the third day after the LAD. Then it stay stable at this level.
2. Compared with AMI group The expression of COX-2 protein in the ischemic border zone of the rat heart was descend after Parecoxib was applied(P<0.05). And the descend was concentration dependent.
3. Compared with AMI group, Parecoxib can improve contractile functions remarkably (LVSP and +dp/dtmax) (P<0.05), while the diastolic function was not changed.
4. Compared with AMI group, the use of parecoxib can not alter Infarct Size(IS) obviously(P>0.05).
5. LAD caused apoptosis in the ischemic border zone of the rat heart, which included morphological changes such as nuclear chromatin condensation and the“ladder pattern”. The use of parecoxib can restrain apoptosis of cardiocytes in the ischemic border zone of the rat heart.
6. Compared with AMI group, ruduce of activity of caspase-3 was found after parecoxib was applied (P<0.05).
7. Compared with AMI group, Reduced expression rate of Bax/Bcl-2 mRNA and protein were found after parecoxib was applied(P<0.05).
CONCLUSIONS:
In the process of AMI, the level of COX-2 in mRNA and protein both rose up, however, Parecoxib can concentration-dependently protect the cardiac myocyte.
The mechanism of the protective effect was probably asocilited with the inhibition of apoptosis of the cardiac myocyte.
Objective:
To investigate the protective effects and mechanisms of jiont use of Trimetazidin and Parecoxib sodium to hearts of acute myocardial infarction of rats .
METHODS :
Eighty Sprague-Dawley rats were randomly divided into five groups. 1, sham group; 2, acute myocardial infarction group (AMI); 3, Trimetazidin group (AMI+TMZ); 4, Parecoxib group (AMI+Parecoxib); 5, Joint use of Trimetazidin and Parecoxib group (AMI+TMZ&Parecoxib). All rats were sacrificed and cardiac function (HR, LVSP, LVEDP, +dp/dtmax, -dp/dtmax)was measured with a Pclab-3804 biological signal processing system on the eighth day. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and Cleaved Caspase-3 protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
RESULTS:
1. Compared with Sham group , AMI group showed increased expression of COX-2 protein (P<0.01). Parecoxib group showed decreased expression of COX-2 protein in comparison with AMI group (P<0.01).
2. Compared with AMI group, the joint use of Trimetazidin and Parecoxib can improve contractile functions remarkably (LVSP and +dp/dtmax) (P<0.05), reduce the infarct size (P<0.05) and lower the apoptosis rates. Specifically, the joint use of Trimetazidin and Parecoxib show a better effect than use alone.
3. Reduced expression of Bax/Bcl-2 mRNA and protein , in addition with the ruduce of activity of caspase-3 and cleaved caspase-3 protein ewere also found in joint group compared with the other groups(P<0.05).
CONCLUSIONS:
The jiont use of Trimetazidin and Parecoxib can effectively improve cardiac dysfunction and reduce infarct size. The mechanism of the protective effect was probably asocilited with the inhibition of apoptosis of the cardiac myocyte .
通过结扎大鼠冠状动脉左前降支(Left Anterior Descending, LAD)造成大鼠急性心肌缺血模型,观察缺血大鼠心肌组织中COX-2表达变化情况。通过给予选择性COX-2抑制剂帕瑞昔布,初步探讨COX-2在急性心肌缺血大鼠心肌组织中所发挥的作用。
方法:
一、为观察COX-2在急性心肌梗死大鼠心肌组织中表达的变化以及发挥的作用,分别取造模成功第2天至第7天的大鼠。测定心功能后迅速处死,取心肌组织,分别检测COX-2蛋白表达,梗死面积,细胞凋亡率。
二、为观察帕瑞昔布钠对心肌的保护作用,大鼠被分为:1、假手术组(Sham):只穿线,不结扎;2、模型组(AMI):AMI+生理盐水腹腔注射或生理盐水灌胃;3、帕瑞昔布钠低剂量组:AMI+Parecoxib (ip.0.2 mg/kg/d);4、帕瑞昔布钠中剂量组:AMI+Parecoxib (ip.0.4 mg/kg/d);5、帕瑞昔布钠高剂量组:AMI+Parecoxib (ip.0.8 mg/kg/d)。从造模第3日至第7日给药,术后第8天检测大鼠心功能(LVSP、LVEDP、+dp/dtmax、-dp/dtmax),测定心脏梗死面积, Bax和Bcl-2基因表达, COX-2、Bax、Bcl-2的蛋白表达,Caspase-3活化以及心肌梗死周边区细胞凋亡率。以观察给予帕瑞昔布钠治疗后,大鼠心肌组织损伤的变化情况。
结果:
1. COX-2蛋白在Sham组大鼠心肌组织中几乎不表达。与Sham组相比,大鼠冠脉左前降支结扎后心肌梗死周边区COX-2蛋白表达升高(P<0.01);随着梗死天数的增加,COX-2蛋白表达逐渐增高,并于第3日达到峰值,此后梗死心肌COX-2蛋白含量稳定于此浓度。
2.帕瑞昔布钠浓度梯度给药后,心梗大鼠心肌细胞中的COX-2表达下降(P<0.05),随着给药浓度的增加,COX-2蛋白表达逐渐下降,说明帕瑞昔布钠能够减少心梗大鼠心肌细胞中COX-2的蛋白表达。
3.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,受到损伤的心肌收缩功能(LVSP、+dp/dtmax)明显恢复,差异具有著性意义(P<0.05);心肌舒张功能(LVEDP、-dp/dtmax)虽有上升趋势,但是差异无显著性意义(P>0.05),且这种改变具有一定的浓度依赖性。
4.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,各组大鼠梗死面积有改变,但是差异不具有显著性意义(P>0.05)。
5.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,大鼠梗死周边区细胞的DNA Ladder条带化程度减弱,且随着给药浓度的增加,心肌细胞Ladder条带化程度持续减弱。
6.心梗大鼠给予不同剂量帕瑞昔布钠五天治疗后,心梗周边区caspase-3的活化程度下降(P<0.05),且随着给药浓度的增加,caspase-3活化程度减弱,差异具有统计学意义(P<0.05)。
7.与AMI组相比,梯度浓度给予帕瑞昔布钠治疗后,Bax/Bcl-2的mRNA和蛋白表达比例均下降(P<0.05);随着给药浓度的增加,Bax/Bcl-2的mRNA和蛋白表达比例逐渐下降(P<0.05)。
结论:
心肌急性缺血过程中,心肌细胞中COX-2的基因水平和蛋白水平均增高。帕瑞昔布钠可以浓度依赖性保护心肌细胞免受心肌缺血缺氧的损伤。其保护急性心肌缺血大鼠心肌细胞的机制可能与抑制缺血组织细胞凋亡有关。
目的:
通过在急性心肌缺血模型中给予抗代谢药曲美他嗪与选择性COX-2抑制剂帕瑞昔布钠,观察他们是否具有协同保护急性心肌梗死大鼠心脏的作用。
方法:
80只雄性SD大鼠随机分为1、假手术组(Sham):只穿线,不结扎;2、模型组(AMI):AMI+生理盐水腹腔注射或生理盐水灌胃;3、曲美他嗪给药组:AMI+TMZ(ig. 20 mg/kg/d);4、帕瑞昔布钠给药组:AMI+Parecoxib (ip. 0.75 mg/kg/d);5、曲美他嗪和帕瑞昔布钠联合给药组:AMI+ TMZ(ig. 20 mg/kg/d)+Parecoxib (ip. 0.8 mg/kg/d)。大鼠实施冠状动脉左前降支结扎后,第3d开始给药,第8d检测大鼠心功能(HR、LVSP、LVEDP、+dp/dtmax、-dp/dtmax),测定心脏梗死面积, Bax和Bcl-2基因表达, COX-2、Bax、Bcl-2的蛋白表达,Caspase-3活化率以及心肌梗死周边区细胞凋亡率。
结果:
1.与假手术组相比,AMI模型组大鼠心肌梗死周边区COX-2蛋白表达明显增高(P<0.01);帕瑞昔布钠治疗组与AMI模型组相比,COX-2表达下降(P<0.01);
2.联合给药治疗组与模型组相比,能显著改善心肌梗死大鼠的心脏收缩功能(LVSP与+dp/dtmax)(P<0.05),并减小心肌梗死面积(P<0.05),心肌梗死周边区细胞的凋亡程度下降。并且联合给药治疗效果优于单独给药。
3.联合给药治疗组与模型组相比,Bax/Bcl-2 mRNA和蛋白表达比例显著降低(P<0.05),Caspase-3活性率下降(P<0.05)。
结论:
帕瑞昔布钠与曲美他嗪联合给药具有一定的协同保护缺血心肌的作用,其机制可能与共同抑制心肌细胞凋亡有关。
Objective:
Cyclo-oxygenase-2 (COX-2) is the enzyme that catalyzes the conversion of arachidonic acid to prostaglandin. A great interest in COX-2 has developed over the years because it`s only induced in cardiomyocytes in response to stress, such as ischaemia and endotoxin, While not present in most normal cells. The ligation of the left coronary artery was performed to detected COX-2 protein levels in the myocardium in the ischemic border zone of the rat heart. Then, a selected COX-2 inhibitor Parecoxib sodium was applied to survey the the effects of COX-2 in ischemia myocardium in AMI rats.
METHODS :
1. All rats were sacrificed after the ligation of the left coronary artery was performed for two to seven days. The heart function was detected by Pc-lab bioinstruments. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
2. To observe the protective effects of parecoxib sodium, ligation of the left coronary artery or sham operation was performed. The rats that underwent ligation were randomly assigned to 5 groups: 1. Sham group; 2. AMI group: AMI+physiological saline; 3. Low dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.2 mg/kg/d); 4. Moderate dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.4 mg/kg/d); 5. High dosage of parecoxib sodium group: AMI+Parecoxib (ip.0.8 mg/kg/d). The heart function was detected by Pc-lab bioinstruments. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
RESULTS:
1. COX-2 protein wan not expression in Sham group. Compared with Sham group , AMI group showed increased expression of COX-2 protein (P<0.01). It rose up gradually and the peak concentration appeared on the third day after the LAD. Then it stay stable at this level.
2. Compared with AMI group The expression of COX-2 protein in the ischemic border zone of the rat heart was descend after Parecoxib was applied(P<0.05). And the descend was concentration dependent.
3. Compared with AMI group, Parecoxib can improve contractile functions remarkably (LVSP and +dp/dtmax) (P<0.05), while the diastolic function was not changed.
4. Compared with AMI group, the use of parecoxib can not alter Infarct Size(IS) obviously(P>0.05).
5. LAD caused apoptosis in the ischemic border zone of the rat heart, which included morphological changes such as nuclear chromatin condensation and the“ladder pattern”. The use of parecoxib can restrain apoptosis of cardiocytes in the ischemic border zone of the rat heart.
6. Compared with AMI group, ruduce of activity of caspase-3 was found after parecoxib was applied (P<0.05).
7. Compared with AMI group, Reduced expression rate of Bax/Bcl-2 mRNA and protein were found after parecoxib was applied(P<0.05).
CONCLUSIONS:
In the process of AMI, the level of COX-2 in mRNA and protein both rose up, however, Parecoxib can concentration-dependently protect the cardiac myocyte.
The mechanism of the protective effect was probably asocilited with the inhibition of apoptosis of the cardiac myocyte.
Objective:
To investigate the protective effects and mechanisms of jiont use of Trimetazidin and Parecoxib sodium to hearts of acute myocardial infarction of rats .
METHODS :
Eighty Sprague-Dawley rats were randomly divided into five groups. 1, sham group; 2, acute myocardial infarction group (AMI); 3, Trimetazidin group (AMI+TMZ); 4, Parecoxib group (AMI+Parecoxib); 5, Joint use of Trimetazidin and Parecoxib group (AMI+TMZ&Parecoxib). All rats were sacrificed and cardiac function (HR, LVSP, LVEDP, +dp/dtmax, -dp/dtmax)was measured with a Pclab-3804 biological signal processing system on the eighth day. The infarct size in each group was checked up by TTC dyeing method. RT-PCR was employed to detect the Bax mRNA and Bcl-2 mRNA, Western Blot was employed to detect the COX-2,Bax,Bcl-2 and Cleaved Caspase-3 protein expression in myocardium. The activation of caspase-3 in each group was measured by Colorimetric Assay Kit , and the apoptosis rates were measured with DNA ladder kit.
RESULTS:
1. Compared with Sham group , AMI group showed increased expression of COX-2 protein (P<0.01). Parecoxib group showed decreased expression of COX-2 protein in comparison with AMI group (P<0.01).
2. Compared with AMI group, the joint use of Trimetazidin and Parecoxib can improve contractile functions remarkably (LVSP and +dp/dtmax) (P<0.05), reduce the infarct size (P<0.05) and lower the apoptosis rates. Specifically, the joint use of Trimetazidin and Parecoxib show a better effect than use alone.
3. Reduced expression of Bax/Bcl-2 mRNA and protein , in addition with the ruduce of activity of caspase-3 and cleaved caspase-3 protein ewere also found in joint group compared with the other groups(P<0.05).
CONCLUSIONS:
The jiont use of Trimetazidin and Parecoxib can effectively improve cardiac dysfunction and reduce infarct size. The mechanism of the protective effect was probably asocilited with the inhibition of apoptosis of the cardiac myocyte .
引文
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12. Tanala G, Quaini F, Sala R, et al. Acute myocardial in humans is associated with activation of prograrnmed myocyte cell death in the surviving portion of the heart. J Mol Cell Cardiol[J], 2004; 28(6): 2005-2016
13. Allen RT, Hunter WJ, Agrawal DK. Morphological and biochemical characterisation racterisation and analysis of apoptosis. J Pharmacol Toxicol Methods[J]. 1997; 37 (3): 215-228
14. Giannessi D, Lazzerini G., Sicari R, et al. Vasoactive eicosanoids in the rat heart: clues to a contributory role of cardiac thromboxane to post-ischaemic hyperaemia. Pharmacol Res[J]. 2007; 26(8): 341-356
15. Sandmann S, Spitznagel H, Chung O, ea al. Effects of calcium channel antagonist mibefradil on haemodynamic and morphological parameters in myocardial infarction- induced cardiac failure. Cardiovasc Res[J], 1998; 39(9): 339–350.
16. Boger RH, Bode-Boger SM, Gutzki FM, et al. Rapid and selective inhibition of platelet aggregation and thromboxane formation by intravenous low dose aspirin in man. Clin Sci[J]. 2003; 84(5): 517–524.
17. Shinmura K, Xuan YT, Tang XL, et al. Inducible nitric oxide synthase modulates cyclo-oxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circ Res[J]. 2002; 90: 602–608.
18. Saito T, Rodger IW, Hu F, et al. Inhibition of COX pathway in experimental myocardial infarction. J Mol Cell Cardiol[J]. 2004; 37: 71–77.
19. Lapointe MC, Mendez M, Leung A, Tao Z, Yang XP. Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in mouse. Am J Physiol Heart Circ Physiol[J]. 2003; 286: 1416–1424.
20. Abbate A, Santini D, Biondi-Zoccai GGL, et al. Cyclooxygenase-2 (COX-2)expression at site of recent myocardial infarction: Friend or foe? Heart[J]. 2004; 90: 440–443.
21. Paris A, Bussani R, Biondi-Zoccai GGL, et al. Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium. Eur Heart[J]. 2005; 26: 2039–2045.
22. Mobert ,Wang M, Cheng Y, FitzgeraldGA. Cardiovascular hazard and non-steroidal anti-inflammatory drugs. Curr Opin Pharmacol[J]. 2005; 5: 204–210.
23. Chandrashekhar Y, Sen S, Anway R, et al. Longterm caspase inhibition ameliorates apoptosis, reduces myocardial troponin-I cleavage, protects left ventricular function and attenuates remodelling in rats with myocardial infarction. J Am Coll Cardiol[J]. 2004; 43: 295–301.
24. Shinmura K, Xuan YT, Tang XL, et al. Inducible nitric oxide synthase modulates cyclo-oxygenase-2 activity in the heart of conscious rabbits during the late phase of ischemic preconditioning. Circ Res[J]. 2002; 90:602–608.
25. Saito T, Rodger IW, Hu F, et al. Inhibition of COX pathway in experimental myocardial infarction. J Mol Cell Cardiol[J]. 2004; 37:71–77.
26. Lapointe MC, Mendez M, Leung A, et al. Inhibition of cyclooxygenase-2 improves cardiac function after myocardial infarction in mouse. Am J Physiol Heart Circ Physiol[J]. 2003; 286:H1416–1424.
27. Wong D, Wang M, Cheng Y, et al. Cardiovascular hazard and nonsteroidal anti-inflammatory drugs. Curr Opin Pharmacol[J]. 2005; 5: 204–210.
28. Abbate A, Limana F, Capogrossi MC, et al. Cyclo-oxygenase-2 (COX-2) inhibition reduces apoptosis in acute myocardial infarction. Apoptosis[J]. 2006; 11:1061–1064.
29. Saito T, Giaid A. Cyclooxygenase 2 and nuclear factor-kappaB in myocardium of end-stage human heart failure. Circulation[J]. 1999; 5:222–227.
30. Schiller NB, Shah PM, Crawford M, et al. Recommendations for quantitation of the left ventricle by two-dimensional echocardiography. American Society ofEchocardiography Committee on Standards, Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr[J]. 1989; 2:358–367.
31. Abbate A, Bussani R, Biondi-Zoccai GGL, et al. Infarct-related artery occlusion, tissue markers of ischaemia, and increased apoptosis in the peri-infarct viable myocardium. Eur Heart[J]. 2005; 26:2039–2045.
32. Degabriele, Dutka DP, Pagano D, et al. Immunocytochemical evidence for inducible nitric oxide synthase and cyclooxygenase-2 expression with nitrotyrosine formation in human hibernating myocardium. Bas Res Cardiol[J]. 2002; 97:409–415.
33. Delgado RM, Nawar MA, Zewail AM, et al. Cyclooxygenase-2 inhibitor treatment improves left ventricular function andmortality in a murinemodel of doxorubicin- induced heart failure. Circulation[J]. 2004; 109:1428–1433.
34. Riendeau D, Percival MD, Boyce S, et al. Biochemical and pharmacological profile of a tetrasubstituted furanone as a highly selective COX-2 inhibitor. Br J Pharmacol [J]. 1997;121:105–117.
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