自体骨髓单个核细胞移植改善心肌梗死并左心功能不全患者血管内皮功能

Autologous bone marrow mononuclear cell transplantation improves vascular endothelial function in patients with myocardial infarction and left ventricular dysfunction

背景：内皮功能障碍与多种心血管疾病危险因素相关,主要体现为一氧化氮的生成减少或功能异常。自体骨髓干细胞移植进行心脏修复具有一定效果,但在治疗早期移植的干细胞对血管内皮细胞功能的影响尚不清楚。目的：探讨自体骨髓单个核细胞经冠状动脉移植后对心肌梗死并左心功能不全患者血管内皮功能的影响。设计、时间及地点：开放性临床实验,于2005-01/2006-12在北京大学第三医院心内科研究室完成。对象：北京大学第三医院同期收治的前壁心肌梗死并已成功再灌注治疗、置入冠状动脉内支架的男性患者16例,年龄33-75岁,按患者意愿分为细胞移植组8例,对照组8例。方法：两组患者均接受标准经皮冠状动脉支架置入和药物治疗,在此基础上,细胞移植组患者抽取自体骨髓液,密度梯度离心法分离骨髓单个核细胞,经导管冠状动脉内注入细胞悬液（12.84±4.10）mL,细胞总数为（1.36±0.44）×10^9个,流式细胞仪测定CD34^＋细胞为（17.75±8.21）×10^6个。分别于细胞移植前后采集两组患者静脉血,制备血浆标本。主要观察指标：细胞移植前后血浆中一氧化氮、血管性血友病因子及前列环素2水平的变化。结果：与对照组比较,自体骨髓单个核细胞移植后24,72h细胞移植组血浆中一氧化氮浓度均明显升高（P=0.015,P=0.03）;血浆中血管性血友病因子、前列环素2水平差异无显著性意义（P〉0.05）。结论：经冠状动脉自体骨髓单个核细胞移植可在短期内提高血浆一氧化氮浓度,且不影响血浆血管性血友病因子及前列环素2水平,提示一定程度上可改善血管内皮舒张功能,且不损伤内皮功能。

BACKGROUND： Endothelial functional disturbance is associated with risk factors of various cardiovascular diseases, mainly showing a decreased production of nitrogen monoxidum or abnormal function. Autologous bone marrow stem cell （BMSC） transplantation for heart repair has a certain effects. However, the effect of transplanted stem cells on vascular endothelial cell function is still unclear in early therapeutic period. OBJECTIVE： To explore the influence of autologous bone marrow mononuclear cells on vascular endothelial function in patients with myocardial infarction and left heart insufficiency following coronary artery transplantation. DESIGN, TIME AND SETTING： The opening clinical study was performed at the Institute of Department of Cardiology, Third Hospital, Peking University from January 2005 to December 2006. PARTICIPANTS： Sixteen patients with anterior myocardial infarction, who underwent reperfusion treatment and intracoronary stent at the Third Hospital, Peking University, were enrolled in this study. All patients aged 33 75 years old were divided into a cell transplantation group （n =8） and a control group （n=8） according to patient＇s will. METHODS： Patients in both groups were subjected to standard percutaneous coronary intervention （PCI） and medical therapy. Subsequently, autologous bone marrow was collected from patients of the cell transplantation group. Bone marrow mononuclear stem cells were harvested using the density gradient centrifugation. Cell suspension （12.84±4.10） mL was infused into the coronary artery via a catheter, about （1.36±0.44）×10^9 cells. CD34^＋ cells were （17.75×8.21）×10^6 using a flow cytometry. Venous blood was harvested from patients of both groups before and after transplantation to prepare plasma samples. MAIN OUTCOME MEASURES： Changes in nitric oxide, von Willebrand disease factor and prostacyclin-2 levels in plasma were measured before and after transplantation. RESULTS： Compared with the control group, plasma nitric oxide concentration was significantly increased in the cell transplantation group at 24 and 72 hours following transplantation （P=0.015, P =0.03）. No significant differences in plasma von Willebrand disease factor and prostacyclin-2 levels were detected （P 〉 0.05）. CONCLUSION： Autologous bone marrow mononuclear cell transplantalion via the coronary artery can elevate plasma nitric oxide concentration and does not affect plasma von Willebrand disease factor and prostacyclin-2 levels. This therapy can improve diastolic function of the vascular endothelium and does not impair the endothelial function.