摘要
目的探讨兔颈动脉行球囊损伤后,骨髓间充质干细胞(BMSC)移植对损伤血管内皮修复和再狭窄的影响。方法建立兔颈动脉粥样硬化狭窄模型48只,随机分成BMSC移植组24只和对照组24只。体外培养BM-SC,携带增强型绿色荧光蛋白(EGFP)的腺病毒转染标记后备用。颈总动脉球囊损伤后,以107个/kg的细胞数经颈外动脉移植到损伤动脉局部,对照组注射等量的PBS液。移植后1周取材行免疫组织化学检测BMSC归巢。移植后2周免疫组织化学染色检测血管内膜血小板-内皮细胞黏附分子(CD31)、α-平滑肌肌动蛋白(SMα-actin)及增殖细胞核抗原(PCNA)的表达;移植后4周行颈总动脉造影检测血管狭窄率,HE染色检测损伤血管新生内膜面积、新生内膜面积/中膜面积的变化。结果 BMSC移植组在术后1周损伤血管的内膜有表达EGFP的BMSC归巢。术后2周BMSC移植组血管内膜有连续性CD31的表达,对照组为阴性;BMSC移植组PCNA的表达较对照组明显降低(23.43%±2.80%比50.49%±3.60%,P<0.05),而BMSC移植组SMα-actin的表达较对照组明显增加(0.437±0.049比0.197±0.032,P<0.01)。术后4周HE结果显示:BMSC移植组血管新生内膜面积(0.103±0.022比0.214±0.024,P<0.01)、新生内膜/中膜面积(0.771±0.096比1.646±0.223,P<0.01)均较对照组减轻;颈动脉造影结果显示:BMSC移植组较对照组血管再狭窄率减轻(39.64%±2.30%比63.31%±2.82%,P<0.05)。结论移植BMSC可促进颈动脉球囊损伤后早期再内皮化和血管平滑肌细胞表型转化,抑制血管新生内膜的增生,减轻了血管再狭窄。
Aim To investigate the effect of bone marrow mesenchymal stem cells （BMSC）transplantation on injured vessels endothelium repair and vascular restenosis after carotid balloon injury in rabbits. Methods 48 rabbits of carotid artery stenosis model were established and randomly divided into BMSC transplantation group （n = 24） and control group （ n = 24）. BMSC were cultured in vitro and transfeeted with recombinant adenovirus-mediated enhanced green fluorescent protein gene. Balloon injured carotid artery of rabbits, meanwhile, BMSC （107/kg） were infused into rabbits injured artery by external carotid artery in BMSC transplantation group, and the same amount of PBS solution were infused into the control group. 1 week after transplantation, BMSC homing were detected by immunohistoehemical techniques. 2 weeks after transplantation, the expression of platelet-endothelial cell adhesion molecule （CD31）, α-smooth muscle aetin and proliferating cell nuclear antigen （PCNA） were detected by immunohistochemieal staining. 4 weeks s after transplantation, the incidences of the vessels stenosis were detected by carotid artery arteriography, the neointimal area and the ratio of the intima/media area were examined by hematoxylin and eosin staining. Results BMSC with GFP homing were detected in injured vessels intima at 1 week after BMSC transplantation. CD31 continues to have expression in intima of BMSC transplantation group, while the control group did not express. The expression of PCNA in BMSC transplantation group were decreased significantly compared with control group（23.43% ± 2.80% vs 50. 49% ± 3.60% ,P 〈 0. 05）. The expression of SM α-actin in BMSC transplantation group were elevated significantly compared with control group （ 0. 437 ± 0.049 vs0.197±0.032, P〈0.01）. Theneointimal area（0.103±0.022 vs 0. 214 ± 0. 024 , P 〈 0. 01） and the ratio of the iutima/media area（0. 771 ± 0. 096 vs 1. 646 ± 0. 223, P 〈 0. 01 ） were significantly decreased in BMSC transplantation group than control group at 4 week. The incidences of the vessels stenosis were decreased compared with control group （ 39.64% ±2. 30% vs 63.31% ± 2. 82% ,P 〈 0.05 ）. Conclusion BMSC transplantation can promote repairing of endothelial and phenotypic transforming of vascular smooth muscle cells after carotid balloon injury in rabbits and inhibits neointima hyperplasia. BMSC transplantation can also reduce the restenosis of injured vessels.
出处
《中国动脉硬化杂志》
CAS
CSCD
北大核心
2013年第1期22-27,共6页
Chinese Journal of Arteriosclerosis
基金
国家自然科学基金资助项目(NSFC30860100)
关键词
骨髓间充质干细胞
再狭窄
再内皮化
Bone Marrow Mesenchymal Stem Cells
Restenosis
Reendothelialization
