基因重组生长激素对心肌缺血-再灌注损伤的抗凋亡作用  

Anti-apoptotic effect of recombinant human growth hormone on myocardial ischemia/reperfusion injury in rats

作　　者：王正军[1] 张海洲[1] 邹承伟[1] 李德才[1] 李红昕[1] 范全心[1] 

机构地区：[1]山东大学山东省立医院心外科,山东济南250021

出　　处：《山东大学学报（医学版）》2007年第6期609-612,615,共5页Journal of Shandong University:Health Sciences

摘　　要：目的:探讨心肌缺血-再灌注后不同时段心肌细胞凋亡的变化规律及基因重组生长激素对心肌细胞凋亡的影响,为临床缺血性心脏病及心脏外科手术中心肌缺血-再灌注损伤的防治提供新的思路和方法。方法:将78只wistar大鼠随机分为心肌缺血-再灌注组(IR组)、心肌缺血-再灌注+基因重组生长激素基础治疗组Ⅰ(IR+rGHⅠ组)、心肌缺血-再灌注+基因重组生长激素冲击治疗组Ⅱ(IR+rGHⅡ组)和假手术对照组(C组)四组,建立心肌缺血-再灌注模型。各组分设再灌注2、4、24和48 h时相点,采用透射电镜观察心肌超微结构的变化,原位末端探针标记测定各组心肌细胞凋亡指数。结果:IR组线粒体不同程度肿胀,结构破坏,嵴排列紊乱甚至断裂,部分线粒体空泡化;在再灌注后的同一时点,IR+rGHⅠ组线粒体结构破坏程度减轻,空泡化不明显,而IR+rGHⅡ组与IR组相比,线粒体结构破坏的程度无明显差别。对照组无心肌细胞凋亡;IR组再灌注2 h开始出现心肌细胞凋亡,24 h达高峰,再灌注后48 h凋亡指数下降;IR+rGHⅠ组与IR组的4个时点分别进行比较,心肌细胞凋亡指数差异显著(P分别<0.05、0.05、0.01、0.01);IR+rGHⅡ组与IR组的4个时点分别进行比较心肌细胞凋亡指数无差别(P>0.05)。结论:术前7 d皮下注射rGH能减少缺血-再灌注引起的心肌细胞凋亡,线粒体结构破坏较轻;而术前30 s给予rGH无此作用。Objective： To probe into changes of the cardiomyocyte apoptotic index and to observe the effect of recombinant human growth hormone（rGH） on cardiomyocyte apoptosis and mitochondria at different times after ischemic-reperfusion（IR）. Methods： Seventy-eight Wistar rats were randomly allocated into the IR group, the IR ＋ rGH Ⅰ group, the IR ＋ rGHⅠ group and a sham operation group（ without I/R injury）. The IR group was given a normal sodium solution subcutaneously each night for 7 days before the experiment; the IR ＋ GH I group was subcutaneously given 0.75 U/kg recombinant hmnan growth hormone each night for 7 days before the experiment; the IR ＋ GHⅠ group was given 1 U/kg recombinant hmnan growth hormone 30 seconds prior to ischemia. TUNEL was used to detect cardiomyocyte apoptosis. Results： The apoptosis cells appeared after 2 hours of reperfusion, increasing to a zenith after 24 hours of repeffusion and then decreasing. The difference of the apoptosis index between the IR group and the IR ＋ rGHⅠ group was statistically significant（ P 〈0.05）, however, that between the IR group and the IR ＋ rGHⅡ group was not. Condusions： Recombinant growth hormone, used for 7 days before ischemic-reperfusion can reduce the number of apoptosis cells and attenuate the damage to mitochondria, however, used 30 seconds prior to ischemia it does not have this effect.

关 键 词：心肌再灌注损伤 细胞凋亡 基因重组生长激素 大鼠 Wistar 

分 类 号：R654.1[医药卫生—外科学] R332[医药卫生—临床医学]