骨髓间充质干细胞移植对肺动脉高压大鼠肺血管重构的影响  

Effect of Transplantation of Bone Marrow Mesenchymal Stem Cells on Vascular Remodeling of Pulmonary Artery in Rats with Pulmonary Arterial Hypertension

作　　者：汪浩文[1,2] 何志旭[3] 尚峰[3] 

机构地区：[1]皖南医学院附属池州医院 [2]池州市人民医院新生儿科,安徽池州247100 [3]贵阳医学院附属医院儿科,贵阳550004

出　　处：《实用儿科临床杂志》2011年第19期1523-1526,共4页Journal of Applied Clinical Pediatrics

基　　金：国家自然科学基金(30560159);教育部"新世纪优秀人才支持计划"(NCET-05-0820)

摘　　要：目的探讨骨髓间充质干细胞(MSCs)移植对野百合碱诱导的肺动脉高压(PAH)大鼠肺血管重构的影响。方法体外分离、培养并纯化SD大鼠骨髓MSCs。健康雄性SD大鼠随机分为3组:正常对照组(n=15)、PAH组(n=20)和MSCs移植组(n=20)。PAH组和MSCs移植组大鼠一次性项背部皮下注射野百合碱(50 mg.kg-1),复制PAH肺血管重建动物模型。3组大鼠在同等条件下饲养。3周后,MSCs移植组大鼠经舌下静脉注射5×109 L-1的经Hoechst 33342标记的MSCs细胞悬液1 mL,PAH组大鼠予等量低糖-Dulbecco改良Eagle's培养液(L-DMEM)注射,正常对照组不做任何处理。移植28 d,观察3组大鼠肺小动脉的显微结构及超微结构的改变。结果 PAH大鼠用MSCs移植28 d后,肺小动脉管壁厚度指标(WD/TD%、VA%)、放射性肺泡计数、肺非肌性小动脉肌化程度均较PAH组显著改善(P<0.01);其肺小动脉的重构及超微结构的血气屏障、线粒体、板层小体等改变均有明显改善。荧光显微镜观察到Hoechst 33342标记的MSCs在肺内定植,且分化成大量新生血管并形成侧支循环,肺动脉重构得到有效逆转。结论 MSCs移植可有效减轻并逆转肺动脉重构的进程,其作用机制是MSCs分化形成新生血管,建立了侧支循环,从而修复野百合碱诱导的肺损伤。Objective To explore the effect of transplantation of bone marrow mesenchymal stem cells （MSCs） on vascular remodeling of pulmonary artery in rats with monocrotaline - induced pulmonary arterial hypertension （PAH）. Methods MSCs were obtained from bone marrow of SD rats, separately, and were cultured, purified and propagated in vitro. Healthy male SD rats were randomly divided into 3 groups ： normal control group（ n = 15 ）, PAH group（ n = 20） and MSCs transplanted group（ n = 20）. The rats in PAH group and MSCs transplanted group were injected respectively a single subcutaneous monocrotaline （50 mg · kg- 1 ） to induce the models of vascular remodeling of pulmonary artery. The rats in 3 groups were fed in the same condition. After 3 weeks,MSCs were signed by Hoeehst 33342 ,and then 5 × 10^6 MSCs cultured in 1 mL phosphate - buffered saline were infused into the rats in MSCs transplanted group by sublingual vein, and the tales doses of low glucose Dulbecco＇s modification of Eagle＇s medium（ L - DMEM） was also injected in PAH group. Nothing was did in normal control group. The microstructure and ultrastructural changes of small vascular were checked and observed at 28 days after transplantation. Results When the MSCs were transplantated into the rats for 28 days, the index of vascular wall thickness （ WD/TD% , VA% ） , radical alveolar count and musculafization of non -muscularited peripheral pulmonary arterioles were all improved significantly than the monocrotaline - induced group（ P 〈 0. 01 ）. Ultrastructural changes of lung, such as blood gas barrier, chondriosome, osmiophilic lamellar body and so on,were improved significantly in MSCs transplanted group. MSCs labelled Hoechst 33342 were observed that they could permanently planted and differentiate into plentiful collateral circulations in lung by fluorescence microscope. The pulmonary arteries remodeling was reversed effectively in MSCs transplanted group. Conclusions Transplantion of MSCs can reverse the progression o

关 键 词：骨髓 间充质干细胞 移植 肺动脉高压 肺血管重构 大鼠 

分 类 号：R725.4[医药卫生—儿科]