骨髓间充质干细胞移植对心肌梗死后心脏功能及损伤血管再狭窄的影响  

Effect of mesenchymal stem cells on cardiac function and restenosis of injuried artery after myocardial infarction

作　　者：石蓓[1] 刘志江[1] 赵然尊[1] 龙仙萍[1] 王冬梅[1] 王正龙[1] 

机构地区：[1]贵州省遵义医学院附属医院心内科,遵义563003

出　　处：《中华医学杂志》2011年第32期2269-2273,共5页National Medical Journal of China

基　　金：国家自然科学基金（30860100）

摘　　要：目的观察骨髓间充质干细胞（MSC）移植改善心肌梗死后心功能的变化，及其治疗的安全性。方法建立兔右侧颈动脉粥样硬化狭窄和心肌梗死早期再灌注模型并行右侧颈动脉球囊损伤，建模后分为MSC移植组和对照组，经耳缘静脉注射MSC或等体积的磷酸盐缓冲液。移植后1周观察MSC的归巢；2周时免疫组织化学染色检测血管和心肌组织中血小板-内皮细胞黏附分子（CD31）的表达；移植后4周颈动脉造影检测血管狭窄程度，HE染色测定新生内膜面积及血管狭窄率，并同步测定心脏功能和心肌梗死面积、计数梗死心肌周围毛细血管密度。以及移植后对球囊损伤血管再狭窄产生的影响。结果细胞移植后1周在梗死的心肌组织和损伤血管内膜均有4’，6-联脒-2-苯基吲哚二盐酸盐（DAPI）标记的MSC归巢。移植后2周MSC移植组的损伤血管内膜见CD31连续性表达，而对照组无表达。与对照组比较（50．5±3．6）％，MSC移植组血管组织增殖细胞核抗原的表达明显降低[（23．4±2．8）％，P〈0．05]。4周时损伤血管的新生内膜面积（0．092±0．009比0．189±0．007，P〈0．05）及血管再狭窄率在MSC移植组[（41．7±3．7）％]明显小于对照组[（61．3±1．6）％，P〈0．05]。与对照组比较，4周时MSC移植组的心功能有所改善，心肌梗死面积缩小[（21．7±2．2）％比（34．3±1．8）％，P〈0．05]，梗死心肌周围新生毛细血管密度明显增加[（33．6±2．0）％比（20．8±2．6）％，P〈0．05]。结论MSC移植在改善梗死心脏功能的同时，对促进损伤血管的再内皮化和减轻新生内膜的增殖可能产生有益作用，从而有助于减轻损伤血管的再狭窄。Objective Although earlier studies have shown that the transplantation of mesenchymal stem cells （MSCs） might improve cardiac functions after myocardial infraction, its role on vascular restenosis after pereutaneous coronary intervention （PCI） remains controversial. The aim of this study was to investigate the effects of MSCs on the restenosis of injured artery following balloon angioplasty in a rabbit model with both myocardial infarction reperfusion and atherosclerotic stenosis cardotid artery by balloon injury. Methods After the animal model was established for myocardial infraction reperfusion and atherosclerotie stenosis eardotid artery by balloon injury, the rabbits received an intravenous transplantation of MSCs. And an equal volume of phosphate buffered solution was administered for the control group. The animal vascular tissue and myocardium tissue were excised at different time points post-transplantation and used to detect the homing of MSCs and the expressions of platelet-endothelial ceil adhesion molecule-1 （CD31） and proliferating cell nuclear antigen （PCNA） by immunohistochemical staining. Four weeks later, vascular restenosis was analyzed by angiography of bilateral carotid arteries and the vascular tissues were used for histological studies. Results At one week post-transplantation, the 4＇, 6-diamidino-2-phenylindole （DAPI）-labeled MSCs could be detected in myocardial infarction and injured intima. And the intimal expression of CD31 was observed at 2 weeks in the MSCs transplantation group. Yet the expression of PCNA was significantly lower in the MSCs transplantation group than that in the control group （50. 5% ± 3.6% vs 23.4% ±2. 8%, P 〈 0. 05）. At 4 week post-transplantation, the neointimal area of injured vessels and the vascular restenosis were significantly lower in the MSCs transplantation group than those in the control group （0. 092 ±0. 009 vs 0. 189 ±0. 007, P 〈0. 05; 41.7 ±3.7 vs 61.3 ± 1.6, P 〈0. 05）. Furthermore the MSCs transplantation group

关 键 词：心肌梗塞 干细胞 再狭窄 内皮 血管 

分 类 号：R542.22[医药卫生—心血管疾病]