老年心肌梗死患者循环血内皮祖细胞数目和功能的变化及其对心功能的影响

目的 比较不同年龄组心肌梗死患者循环血内皮祖细胞（EPCs）数目及功能的差异,分析蛋白激酶B（Akt）和间质细胞源因子1（SDF-1）表达的差异,探讨老年患者EPCs修复梗死心脏功能的可能机制及临床意义.方法 抽取老年心肌梗死患者（n=26）和中青年心肌梗死患者（n=24）动脉血8 ～10 ml,流式细胞仪检测各组EPCs含量,酶联免疫吸附法检测Akt及SDF-1表达变化情况;利用冠状动脉左前降支结扎术制备大鼠心肌梗死模型后,尾静脉注射老年EPCs、中青年EPCs（1×107/200 ml）或等体积盐水（PBS组）,观察终点时间为28 d,超声心动评价心脏功能,荧光显微镜下观察EPCs在梗死心脏的归巢情况,免疫荧光法计数缺血心肌局部血管数量.结果 老年心肌梗死患者循环血EPCs数量明显少于中青年组（47.23％±14.92％比89.76％ ±7.27％,P＜0.001）;心肌梗死后老年组Akt磷酸化水平和SDF-1表达水平明显低于中青年组（Akt：19.04％±6.41％比43.96％±15.91％;SDF-1：25.81％ ±6.32％比64.04％±16.35％,均为P＜0.001）.将EPCs移植至梗死大鼠后,移植的老年EPCs在梗死心脏的归巢数量明显少于移植的中青年EPCs（3.69±1.97/mm2比12.01 ±5.44/mm2,P ＜0.001）.移植老年EPCs的大鼠梗死心脏的血管密度明显少于移植中青年EPCs的大鼠（42±9/mm2 比96±15/mm2,P ＜0.001）.移植老年EPCs组心功能指标[左心室射血分数（LVEF）和左心室缩短分数（LVFS）]显著低于移植中青年EPCs组（LVEF：58.1％±5.0％比73.8％±7.9％;LVFS：35.4％±3.8％比59.0％±7.6％.均为P＜0.001）.结论 老年心肌梗死患者的循环血EPCs数量及其修复功能均不如中青年患者,可能与Akt-SDF-1信号通路受损有关.

Changes in the number and function of circulating blood endothelial progenitor cells in the elderly patients with acute myocardial infarction and its effects on the infarcted heart function

Objective To explore the mechanism and its clinical significance of the effects of endothelial progenitor cells （EPCs） in the elderly patients with acute myocardial infarction （AMI） on infarcted heart repair through comparison of the number and function of EPCs between different aged patients with AMI and analysis of variation of Akt and SDF-1 expression. Methods The 8-10 ml of arterial blood were extracted from the eider AMI patients （ n = 26） and the young and middle-aged AMI patients （ n = 24）. Circulating blood endothelial progenitor cells （EPCs） was evaluated by flow cytometry analysis （FACS）.The expressions of Akt and SDF-1 in EPCs were determined by enzyme-linked immunosorbent assay （ELISA）. MI was induced in the inbred Lewis rats by left anterior descending artery ligation. of EPCs from the eider MI patients or the young and middle-aged AMI patients or equal volume of saline were immediately injected into the MI rats through the tail veins. At 28 days post-operation, cardiac function were measured by echocardiography. The number of EPCs was observed in the infarcted heart under a fluorescence microscope. The vascular density was examined by immunofluorescence （IF）. Results FACS revealed the number of circulating blood EPCs in the elder AMI patients was significantly smaller than in the young and middle-agedAMI patients （47.23% ±14.92% vs. 89.76% ±7.27%, P〈0.001）. ELISA showed that the expression levels of Akt and SDF-1 were notably lower in the elder AMI patients than in the young and middle-aged AMI patients （Akt： 19.04% ±6.41% vs. 43.96% ±15.91% ; SDF-1 ： 25.81%±6.32% vs. 64.04% ± 16.35% , both P 〈 0. 001 ）. After these cells were transplanted into the infarcted rats, fluorescence microscopic examination showed that the number of the engrafted elder EPCs homing into the infarcted hearts was significantly less than that of the engrafted young and middle-aged EPCs [ （3.69± 1.97） mm2 vs. （ 12. 01 ± 5.44） mm2 , P 〈 0. 001 ]. IF showed that the vascular density was evidently smaller in the rats receiving the eider EPCs therapy than in the rats receiving the young and middle-aged EPCs therapy （42± 9/mm vs. 96 ± 15/mm2 , P 〈 0. 001 ）. Echocardiography showed that the cardiac function indexes （LVEF and LVFS） were significantly lower in the rats receiving the elder EPCs therapy than in the rats receiving the young and middle-aged EPCs therapy （LVEF： 58.1%±5.0% vs. 73.8% ± 7.9%; LVFS： 35.4% ±3.8% vs. 59.0% ±7.6%, P 〈0.001）. Conclusions The number and function of circulating endothelial progenitor cells in elderly patients with MI are not as good as those in young and middle-aged, which may be associated with impaired Akt-SDF-1 pathway.