同源异体骨髓间充质干细胞移植对大鼠实验性肺动脉高压的治疗作用  

Allogeneic bone marrow mesenchymal stem cells transplantation has therapeutic effect on pulmonary arterial hypertension in rats

作　　者：汪浩文[1,2] 何志旭[3,4] 尚峰[3,4] 王志华[3,4] 米蔷[3,4] 

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]贵阳医学院干细胞研究中心 [4]贵阳医学院附属医院儿科,贵州贵阳550004

出　　处：《临床儿科杂志》2010年第5期477-481,共5页Journal of Clinical Pediatrics

基　　金：国家自然科学基金资助项目(No.30560159);教育部新世纪优秀人才支持计划项目(No.NCET-05-0820);贵州省科技攻关项目(No.黔科字2008-7号)

摘　　要：目的探讨同源异体骨髓来源的间充质干细胞(mesenchymal stem cells,MSCs)移植对大鼠实验性肺动脉高压的治疗效果及作用机制。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)、肺动脉高压组(n=30)、MSCs移植组(n=20)。肺动脉高压组和MSCs移植组大鼠一次性项背部皮下注射野百合碱(50 mg/kg),复制肺动脉高压模型。三组大鼠同等条件饲养。3周后,MSCs移植组大鼠经舌下静脉注射5×106/ml的经Hoechst 33342标记的MSCs细胞悬液1 ml,肺动脉高压组大鼠予等量L-DMEM液,正常对照组不作任何处理。移植后28 d,观察三组大鼠的平均肺动脉压力(mPAP)、右心指数、血气及肺小动脉的微观结构的改变。结果肺动脉高压模型大鼠用MSCs移植28 d后,该组动物生存率为100%,平均肺动脉压力明显降低、右心指数下降,动脉血气指标等均有明显改善,与肺动脉高压组相比差异有统计学意义(P<0.01)。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野百合碱诱导的肺动脉高压的进程,其治疗作用机制可能与MSCs分化形成新生血管和改善肺小动脉血管重构有关。Objective To explore the mechanisms and therapeutic effect of bone marrow-derived mesenchymal stem cells（MSCs） on rat models with pulmonary arterial hypertension（PAH）.Methods MSCs were obtained from bone marrow of Sprague-Dawley（SD） rats,and were separated,cultured,purified and propagated in vitro.Healthy male SD rats were randomly divided into 3 groups,normal control group（n = 15）,PAH model group（n = 30）,MSCs transplanted group（n = 20）.The rats of the PAH model group and MSCs transplanted group were injected with a single subcutaneous monocrotaline（50 mg/kg） to induce the models of PAH.Rats of the three groups were fed under the same condition.After 3 weeks,MSCs were signed by Hoechst 33342.Then 5 × 106 MSCs cultured in 1 ml phosphate-buffered saline was infused into the rats in MSCs transplanted group by sublingual vein.The same dose of L-DMEM was also injected in PAH model group.Mean pulmonary arterial pressure,right ventricle hypertrophy index,blood gas analysis and the microstructure changes of small pulmonary vascular were checked and observed on day 28.Results When the MSCs were transplanted into the rats with PAH after 28 days,the survival rate of MSCs transplanted group is 100% and the mean pulmonary arterial pressure decreased obviously,right ventricle hypertrophy index degraded too,the results of blood gas analysis and the pulmonary arteries remodeling,were improved significantly in MSCs transplanted group.The changes were better than that in PAH model group with statistical significance（P 0.01）.MSCs labelled Hoechst 33342 were observed to permanently planted and differentiated into plentiful collateral circulations in lungs by fluorescence microscope.The pulmonary arteries remodeling was attenuated obviously in MSCs transplanted group.Conclusions These results indicated that MSCs transplantation can reduce and reverse the progression of PAH.The possible mechanism is that MSCs cells can repair the monocrotaline-damaged lungs by collateral circulation formation,retroconv

关 键 词：骨髓 间充质干细胞 肺动脉高压 治疗 

分 类 号：R543.2[医药卫生—心血管疾病]