摘要
目的:缺血引起的心肌能量供应不足是心肌细胞凋亡主要的因素之一,观察补充外源性能量磷酸肌酸对缺血心肌细胞凋亡和心功能的影响。方法:实验于2003-04/06在解放军总医院老年心血管病研究所实验室完成。选用SD大鼠50只,按随机数字表法分为3组:①磷酸肌酸组19只,结扎左冠状动脉制作心肌梗死模型,结扎前30min按200mg/kg的剂量腹腔注射磷酸肌酸1次。②缺血对照组21只,心肌缺血方法同磷酸肌酸组,结扎前30min腹腔注射相同体积的50g/L葡萄糖注射液1次。③正常对照组10只,仅在冠状动脉下穿线,不结扎冠状动脉,其余同缺血对照组。结扎冠状动脉6h后,取各组大鼠心脏标本做石蜡切片,缺口末端标记法染色,高倍镜下计数心肌细胞凋亡指数,凋亡指数=凋亡心肌细胞数/心肌细胞总数;取心脏标本前,测左心室收缩压、舒张末压和压力变化速度,并进行组间比较。结果:磷酸肌酸组大鼠造模时死亡9只;缺血对照组造模时死亡10只,造模成功后6h内死亡1只,进入结果分析共30只大鼠,每组10只。①缺血对照组大鼠的左心室舒张末压显著高于正常对照组[(13.9±5.3vs.2.8±3.2)mmHg(P<0.01)],左心室压力变化速度显著低于正常对照组[(705.8±111.7vs.1141.7±94.5)mmHg/s(P<0.01)];磷酸肌酸组大鼠的左心室舒张末压显著低于缺血对照组[(8.9±3.5)mmHg(P<0.05)];左心室压力变化速度显著高于缺血对照组[(841.5±76.1)mmHg/s(P<0.01)];左心室收缩压与缺血对照组差异无显著性意义(P>0.05)。②磷酸肌酸组大鼠的心肌细胞凋亡指数显著低于缺血对照组(0.203±0.054vs.0.278±0.052,P=0.006)。结论:补充外源性能量磷酸肌酸可以减少缺血后心肌细胞凋亡,并改善心功能,磷酸肌酸抑制缺血心肌细胞凋亡可能是改善心肌梗死后心功能的主要作用途径之一。
AIM： The myocardium energy insufficiency caused by ischemia may induce the myocardial apoptosis, this paper is aimed to evaluate the effect of supplying ischemic myocardium with exogenous high-energy agents （creatine phosphate, CP） on cardiomyocytic apoptosis and cardiac function.
METHODS： The experiment was carded out in the laboratory, Institute of Geriatric Cardiology, Chinese PLA General Hospital from April to June in 2003. Fifty SD rats were randomized to three groups.（1）CP group （n =19）： The model of myocardial infarction was made by surgically ligating left main coronary artery in SD rats. The rats were administrated with. CP （200 mg/kg） half one hour before operation（2）Ischemic control group （n =21 ）： The rats were injected with equal volume of placebo （50 g/L）, and 30 minutes later the model was established as above group.（3）Normal control group （n = 10）： The rats only received thread-through of coronary artery but without ligation, while other managements were identical with that of ischemic control group. All the rats, with their left ventricle functions having been measured including left ventricular systolic pressure （LVSP）, left ventricular end-diastolic pressure （LVEDP） and the maximum rate of left intraventricular pressure change （LVdp/dt）, were killed six hours after operation. The left ventricles were harvested for paraffin slices. Cardiomyocytic apoptosis were detected by TdT-mediated dUTP-biotin nick end labeling （TUNEL） method. Apoptosis index was calculated in high magnification field of microscopy according to the formula of the number of apoptosis cells/total number of myocardial cells.
RESULTS： There were 9 deaths in CP group, 10 deaths in ischemic control group during the model establishment, additionally 1 loss within 6 hours after modeling, thus totally 30 rats were involved in the result analysis, each group contained 10 rats. （1）Compared with normal control group, LVEDP in ischemic control group increased significantly [（13.9±5.3 vs. 2.8±3.2） mm Hg, P 〈 0.01], and LVdp/dt decreased significantly [（705.8±111.7 vs. 1 141.7±94.5） mm Hg/s, P 〈 0.01]; In CP group, the LVEDP was significantly lower and LVdp/dt was significantly higher than that of ischemic control group [（8.9±3.5） mm Hg, P 〈 0.05; （841.5±76.1） mm Hg/s, P 〈 0.01]. LVSP did not change significantly （P 〉 0.05）. （±）Apoptosis index of cardiomyocytes in CP group decreased significantly, compared with that in ischemic control group （0.203±0.054 vs. 0.278±0.052, P =0.006）.
CONCLUSION： The therapy of supplement to ischemic myocardium with exogenous CP can improve cardiac function, which is the possible action approach of CP to inhibit cardiomyocytic apoptosis.
出处
《中国组织工程研究与临床康复》
CAS
CSCD
北大核心
2007年第25期4902-4905,共4页
Journal of Clinical Rehabilitative Tissue Engineering Research
