摘要
目的 :研究卡维地洛对缺血再灌注心肌细胞凋亡及bcl 2、bax基因表达的影响 ,探讨卡维地洛抑制缺血再灌注心肌细胞凋亡的可能分子机制。方法 :结扎Wistar大鼠左冠状动脉前降支 (LAD) ,建立大鼠缺血再灌注动物模型。 30只大鼠分 3组 (每组 10只 ) :卡维地洛组 (卡维地洛治疗 )、缺血再灌注组和假手术组。用Tunnel法检测心肌细胞凋亡 ,并用光学显微镜进行细胞计数 ,免疫组化和原位杂交法检测bcl 2、bax基因表达 ,并利用图像分析系统检测二者的平均光密度值 (A值 ) ,进行定量分析。结果 :心肌细胞凋亡数在缺血再灌注组、假手术组和卡维地洛组分别为 36 .8± 9.0、0 .2± 0 .1和 9.5± 3.0 ,各组间差异有统计学意义 (P <0 .0 1)。缺血再灌注组、假手术组和卡维地洛组的bcl 2mRNAA值分别为 0 .0 6± 0 .0 1、0 .0 8± 0 .0 1和 0 .0 9± 0 .0 1,bcl 2蛋白平均A值分别为0 .0 8± 0 .0 2、0 .14± 0 .0 1和 0 .15± 0 .0 3,卡维地洛组与缺血再灌注组相比差异无统计学意义 (P >0 .0 5 ) ;缺血再灌注组bax蛋白的平均A值为 0 .13± 0 .0 2 ,假手术组为 0 .0 7± 0 .0 1,卡维地洛组为 0 .0 6± 0 .0 1,卡维地洛组与缺血再灌注组相比差异有统计学意义 (P <0 .0 5 ) ,bcl 2 /bax蛋白比值在缺血再灌注组、假手术组和卡?
Objectives:To study effects of carvedilol on cardiomyocyte apoptosis following ischemia-reperfusion in vivo and on bcl-2 and bax gene expression.Method:The left anterior descending artery in Wister rats was ligated to establish ischemia-reperfusion model. The animals were divided into three groups: carvedilol treatmeid group, control group and sham- operated group. The numbers of apoptotic cardiomyocyte was determined by Tunnel staining. Immunohistochemistry and in situ hybridization histochemistry (ISHH) were used to monitor mRNA as well as protein of bcl-2 and bax. Image processing system was used to quantitatively dispose the positive metric substances of both immunohisochemistry and ISHH through the average optical density (A) value.Result:The number of the apoptotic cells were 36.8± 9.0 ( control group), 0.2± 0.1(sham operated group) and 9.5± 3.0 (carvedilol treatmend group) in each visual field respectively with mark significance (P< 0.01) . There is no obvious influence of carvedilol on bcl-2 gene expression in rat cardiomyocyte following ischemia-reperfusion [protein: ( 0.15± 0.03) vs( 0.14± 0.01), P> 0.05; mRNA: ( 0.09± 0.01)vs( 0.08± 0.01), P> 0.05]. Bax gene expression was decreased very significantly in carvedilol treated group as compared with the control group [( 0.06± 0.01)vs( 0.13± 0.02),P< 0.01]. Bcl-2/bax ratio was increased by carvedilol significantly as compared with the control group [( 2.50± 0.26)vs( 1.07± 0.14), P< 0.05].Conclusions:Carvedilol may inhibit cardiomyocyte apoptosis following ischemia and reperfusion; bcl-2/bax ratio enhanced by bax gene expression inhibition may be the mechanism.
出处
《临床心血管病杂志》
CAS
CSCD
北大核心
2004年第4期220-222,共3页
Journal of Clinical Cardiology
