摘要
【目的】探讨人脐血单个核细胞移植对急性心肌梗死后血管再生的作用。【方法】雄性Wistar大鼠60只随机分为对照组(心肌梗死)和移植组(心肌梗死+细胞移植)各30只。结扎冠状动脉左前降支制作大鼠急性心肌梗死模型,以羟乙基淀粉沉淀加密度梯度离心的方法制备人脐血单个核细胞,并以5-溴脱氧尿核苷(BrdU)标记细胞。移植组大鼠模型制作成功后即在梗死区周边注射经分离并标记的人脐血单个核细胞混悬液(2×105/μL),在对照组相同位置注入等量达尔伯克必需培养基(DMEM)。移植4周后用左心导管检测血流动力学改变,并取心脏组织行抗第Ⅷ因子(vWF)和BrdU免疫组化染色,观察毛细血管密度、移植细胞成活情况。并分别在移植后第4天、第7天、第14天、第28天取梗死周边区组织作血管内皮生长因子(VEGF)RT-PCR的半定量研究。【结果】移植组移植的单个核细胞可在梗死心肌内存活。移植组比对照组心功能明显改善,左心室舒张末压(LVEDP)明显降低(21.08±8.10)mmHgvs(30.82±9.59)mmHg,P<0.05;左心室内压力最大上升速率(+dp/dtmax)明显增快(4.29±1.27)mmHg/msvs(3.24±0.75)mmHg/ms,P<0.05;最大下降速率(-dp/dtmax)亦显著提高(3.71±0.79)mmHg/msvs(3.00±0.49)mmHg/ms,P<0.05。移植组梗死区周边毛细血管数显著增加(5.7±0.3)/HPvs(2.3±0.4)/HP,P<0.01。VEGFmRNA表达在移植组于第7天明显增加,并持续至第28天,对照组于第4天及第7天可见少量表达,第14天与第28天明显减弱,两组差异有统计学意义(P<0.01)。【结论】人脐血干细胞在未使用免疫抑制剂的条件下可成功移植到大鼠急性心肌梗死区,改善急性心肌梗死大鼠心功能,促进新生血管形成。
[Objective ] Vascular endothelial growth factor （VEGF） is the most potent aniogenic factor. This study aimed to elucidate the possible role of angiogenesis on the repair of myocardial infarction after human umbilical cord blood mononuclear cells transplantation. [Methods] 60 male Wistar rats were randomized into two groups： （1） control group （acute myocardial infarction, n=30）, （2） transplantation group （acute myocardial infarction plus cell transplantation, n=30）. Acute myocardial infarction model was established by ligating rats＇ left anterior descending artery. Thereafter 2×10^5/μL human umbilical cord blood mononuclear ceils were injected into the margin area of infarction immediately,while the control group were injected by vehicle. Assessment of left ventricular function was carried out by hemodynamic measurements 4 weeks post acute myocardial infarction, meanwhile the rats were sacrificed for immunohistochemistric examinations. The VEGF expression was assessed by RT-PCR at 4th, 7th, 14th and 28th days post-transplantation. [Results] The transplanted human umbilical cord blood mononuclear cells survived. Compared with control group, the cell transplantation rats showed a significant reduction of left ventricular end-diastolic pressure（21.08±8.10）mmHg vs （30.82±9.59）mmHg （P〈 0.05）; and showed an increase of ±dp/dtmax（4.29±1.27）mmHg/ms vs （3.24±0.75） mmHg/ms （P〈 0.05） and -dp/dtmax（3.71±0.79） mmHg/ms vs （3.00± 0.49） mmHg/ms （P〈 0.05）, and showed a significant increase of microvessles within the boundary of infarcted myocardium （5.7±0.3）/HP vs （2.3±0.4）/HP（P〈 0.01）. The expression of VEGF was markedly higher from 7th days post-transplantation and maintained for 28 days in comparison with the control group （P〈 0.01）. [Conclusions] Human umbilical cord blood mononuclear cells transplantation without immunosuppresant can improve the heart function and promote angiogenesis in acute myocardial infarction rats.
出处
《中山大学学报（医学科学版）》
CAS
CSCD
北大核心
2006年第4期391-395,共5页
Journal of Sun Yat-Sen University:Medical Sciences
基金
广东省科技厅计划基金资助项目(2003C30603)
广东省自然科学基金资助项目(5001680)
关键词
心肌梗死
脐带血
细胞移植
血管内皮生长因子
myocardial infarction, cell transplantation
human umbilical cord blood
VEGF
