Carvedilol对大鼠实验性缺血再灌注心肌细胞凋亡的影响

EFFECT OF CARVEDILOL ON CARDIOMYOCYTE APOPTOSIS IN THE EXPERIMENTAL ISCHEMIA/REPERFUSION RAT

研究 Carvedilol对缺血再灌注心肌细胞凋亡及 Bcl- 2、Bax蛋白表达的影响 ,探讨 Carvedilol抑制心肌细胞凋亡的可能机制。结扎 Wistar大鼠左冠状动脉前降支 (L AD) ,建立大鼠缺血再灌注动物模型。采用末端标记原位细胞凋亡法检测心肌凋亡细胞 ,并利用光学显微镜进行细胞计数 ;免疫组化法检测 Bcl- 2和 Bax蛋白表达 ,并利用图象分析系统检测二者的平均光密度值 ,进行定量分析。结果显示手术组心肌细胞凋亡数为 37.5 3± 9.2 2个 /视野 ,假手术组 0 .18± 0 .91个 /视野 ,治疗组为 7.6 3± 4.0 5个 /视野。各组间有显著差异 (P<0 .0 5 ) ;手术组 Bcl- 2蛋白平均光密度值为 0 .14± 0 .0 1,假手术组为 0 .0 9± 0 .0 2 ,治疗组为 0 .14± 0 .0 2 ,手术组和治疗组与假手术组相比均有显著差异 (P<0 .0 5 ) ,治疗组与手术组相比无显著差异(P>0 .0 5 ) ;手术组 Bax蛋白平均光密度值为 0 .10± 0 .0 2 ,假手术组为 0 .0 6± 0 .0 1,治疗组为 0 .0 7± 0 .0 1,手术组与治疗组、假手术组相比有显著差异 (P<0 .0 5 ) ,治疗组与假手术组相比无显著差异 (P>0 .0 5 )。结果表明 Carvedilol有显著抗缺血再灌注心肌细胞凋亡作用 ,其作用机制可能与抑制 Bax基因的蛋白表达 ,使 Bcl- 2基因表达的蛋白功能相对增强 ,Bcl-

The objective of this study is to investigate the effect of carvedilol on cardiomyocyte apoptosis, expression of Bcl 2 and Bax in ischemia/reperfusion heart and the possible mechanism of carvedilol on inhibiting cardiomyocyte apoptosis. The left anterior descending branch of coronary artery was ligated to the ischemia/reperfusion heart model in Wistar rat; the apoptotic cardiomyocyte is shown by in situ end labeling method and the number of apoptotic cardiomyocyte is counted under optical miscroscopy; expression of Bcl 2 and Bax is shown through immunohistochemistrial method and the value of mean optical density is monitored with computer assisted image analysis. The result shows the number of apoptotic cardiomyocyte per visual field is 37 53±9 22 in operating group, 0 18±0 91 in sham operating group, 7 63±4 05 in treated group. The variance is significant among three groups( P <0 05). The mean optical density of Bcl 2 protein is respectively 0 14±0 01 in operating group, 0 09±0 02 in sham operating group, 0 14±0 02 in treated group; There is a significant meaning between operating group or treated group against sham operating group( P <0 05), but no significance between treated group and operating group( P >0 05). The value of mean optical density of Bax protein is respectively 0 01±0 02 in operating group, 0 06±0 01 in sham operating group, and 0 07±0 01 in treated group. The significance exists between operating group and treated group or sham operating group( P <0 05), but no significance between treated group and sham operating group( P >0 05). It is conecluded that carvedilol has obvious anti apoptotic effect on cardiomyocyte in ischemia/reperfusion heart, and the possible mechanism is by inhibiting expression of Bax gene to raise the ratio of Bcl 2/Bax protein.\;