骨髓间充质干细胞治疗实验性肺动脉高压后肺组织结构的变化  

Changes of lung tissue and structure on bone marrow mesenchymal stem cells transplantation to treat the experimental pulmonary arterial hypertension in rats

作　　者：何志旭[1,2] 汪浩文[1] 尚峰[1] 杨红宇[1] 崔冬冰[1] 杨燕[1] 

机构地区：[1]贵阳医学院干细胞研究中心 [2]贵阳医学院附属医院儿科,贵州贵阳550001

出　　处：《中国病理生理杂志》2009年第10期1907-1911,共5页Chinese Journal of Pathophysiology

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资助项目(No.NCET-05-0820);贵州省高校自然科学基金资助项目(No.黔科教2005-7号)

摘　　要：目的:探讨骨髓间充质干细胞(MMSCs)移植治疗肺动脉高压(PAH)后肺组织超微结构的变化。方法:取SD大鼠的骨髓,经贴壁筛选法体外培养并纯化MMSCs,用Hoechst33342荧光染料标记。实验动物随机分为3组:MMSCs移植治疗组(M组)、肺动脉高压模型组(H组)和正常对照组(C组)。M组采用野百合碱(50mg·kg-1)注射复制PAH模型成功后3周经舌下静脉移植5×109cells/LMMSCs细胞悬液1mL;H组复制PAH模型后3周移植1mLL-DMEM细胞培养液,C组在同时间注射等量L-DMEM液。饲养4周,观察各组动物一般情况、生存率、右心室收缩压、右心指数及肺小动脉的微观结构和超微结构的改变。结果:实验动物移植MMSCs后,生存状况明显改善,食欲及活动增加,毛色顺滑、光亮,动物存活率为100%;而模型组动物活动明显减少、食欲下降,消瘦,体重下降或不增,在1月内相继死亡,死亡率为100%。各项指标检测结果显示,MMSCs移植组(M组)大鼠较单纯肺动脉高压组(H组)右心室收缩压明显降低[移植组为(32.20±2.32)mmHg,而模型组为(48.30±1.56)mmHg,两者相比差异显著,P<0.05],右心指数下降[移植组为(38.80±3.24)%,模型组为(45.10±3.43)%,二者相比差异显著,P<0.05],肺小动脉的重建和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,其结果接近正常对照组。结论:MMSCs移植后可通过形成新生血管建立侧枝循环,有效减轻野百合碱诱导的肺动脉高压和肺组织病变程度。AIM： To investigate the changes of lung tissue and structure on bone marrow mesenchymal stem cells （MMSCs） transplantation to treat the pulmonary arterial hypertension （PAH） in rats. METHODS： MMSCs cells were collected from bone marrow of SD rat＇ s femoral＇ s tibial bones, mix cultured with Hoechst 33342 fluorescence dye in vitro. Sixty healthy male Sprague- Dawley rats （weighing 180 g±5 g） were randomly divided into 3 groups： normal control group （ group C）, MMSCs transplanted group （ group M） , pulmonary model group （ group H）. The rats of the two latter groups were given a single subcutaneous monocrotaline （50 mg/kg） to induce the model of PAH. The rats of normal control group were injected respectively a single subcutaneous isotonic Na chloride （6 mL/kg）. The three groups were fed in the same condition. After 3 weeks, 5 × 10^9 cells/L MMSCs with 1 mL phosphate - buffered saline were infused into the rats respectively in group M by sublingual vein and 1 mL L - DMEM was administered in group H. Nothing was given to group C. The viability, right ventricle systolic pressure （ RVSP）, right ventricle hypertrophy index, the microstrueture and ultrastructural changes of small pulmonary vascular were observed after 28 d. RESULTS： The viability of administrated MMSCs 28 d after PAH was 100% in transplanted group, and it nearly completely prevented the increase in right ventricular systolic pressure （RVSP） compared to PAH alone [ （32. 20 ±2. 32）mmHg vs （48. 30 ± 1.56）mmHg, respectively, P 〈 0. 05 ], fight ventricle hypertrophy index also degraded （ 38. 80% ± 3.24% vs 45.10% ± 3.43%, respectively, P 〈 0.05 ）. The pulmonary arteries remodeling and uhrastructural changes of lung, such as blood gas barrier, chondriosome, osmiophilic lamellar body and so on, were improved significantly in MMSCs transplanted group. The changes were similar to the results of normal control group, but they were better than that in pulmonary arterial hypertension model gr

关 键 词：肺动脉高压 骨髓间充质干细胞 野百合碱 

分 类 号：R563.3[医药卫生—呼吸系统]