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脐血间充质干细胞移植对大鼠肺动脉高压的治疗作用研究

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2013年第3期
页码:
301-306
栏目:
基础研究
出版日期:
2013-06-25

文章信息/Info

Title:
Umbilical cord blood mesenchymal stem cells transplantation in treatment of pulmonary hypertension in rats
作者:
石曌玲1; 王 浩1; 范 芳1; 武小寓1; 王 博2; 王跃民3; 孙 新1
(第四军医大学：1.西京医院儿科，2.西京医院老年病科，3.基础医学院生理学教研室，陕西 西安 710032)
Author(s):
SHI Zhaoling1;  WANG Hao1;  FAN Fang1;  WU Xiaoyu1;  WANG Bo2;  WANG Yue min3;  SUN Xin1
(1.Department of Pediatrics, Xijing Hospital, 2.Department of Geriatrics, 3.Department of Physiology, Fourth Military Medical University, Xi’an 710032, Shaanxi, China)
关键词:
肺动脉高压; 脐带血; 间充质干细胞; 细胞移植; 大鼠
Keywords:
pulmonary hypertension;  umbilical cord blood;  mesenchymal stem cells(MSCs);  rat
分类号:
R543.2
DOI:
-
文献标识码:
A
摘要:
目的:观察脐血间充质干细胞（mesenchymal stem cells，MSCs）移植对SD大鼠肺动脉高压(PAH)的治疗作用。方法:将60只健康雄性SD大鼠随机分为4组，每组15只（n=15），即①正常对照组：不做任何处理；②模型组：以腹主动脉-腔静脉瘘分流术(abdominal aortocaval fistula shuning，A-VF)+单野百合碱(monocrotaline，MCT)注射建立大鼠PAH模型，故也可称为A-VF+MCT组；③干细胞移植组：在建立PAH模型后4周，经尾静脉注射Hoechst 33342荧光染料标记的脐血MSCs，故此组也可称A-VF+MCT+MSCs组；④培养液对照组：在建立PAH模型后4周，经尾静脉注射培养脐血MSCs的培养液，故此组也可称为A-VF+MCT+培养液组。4周后以右心导管法测定平均肺动脉压(mPAP)、右心室肥厚指数［RVHI=RV/(LV+S)］、肺小动脉中层厚度占血管外径的百分比［MA(%)］和血管壁中层横截面积占血管总横截面积的百分比［MA(%)］，观察肺小动脉重构情况。检测血流动力学、肺小动脉重塑及脐血MSCs的定植情况。结果: 与正常对照组比较，造模实验证实，4周后A-VF+MCT组大鼠可形成典型的PAH，8周后mPAP明显增高，动脉中膜明显增厚，右心室出现明显肥厚；而AVF+MCT+MSCs组大鼠mPAP、RV/(LV+S)、MT%和MA%均显著下降（P<0.01）。PAH大鼠死亡率从66.7%下降到13.3%。荧光显微镜观察显示脐血MSCs已成功定植到肺血管内膜。结论:以A-VF+MCT建立的大鼠PAH模型可形成重度PAH。脐血MSCs移植能显著降低肺动脉压力，减轻肺小动脉重构及右心室肥厚，显著降低PAH大鼠的死亡率。
Abstract:
AIM:To establish the pulmonary arterial hypertension (PAH) animal model by arterialvein shunting combining with injection of monocrotaline (MCT) and to observe the therapeutic effects of mesenchymal stem cells (MSCs) from umbilical cord blood on pulmonary arterial hypertension in SpragueDawleye (SD) rats. METHODS: For establishment of the animal model, 60 healthy male SD rats were randomly divided into 4 groups:①normal control group (n=15): The rats were given no treatment; ②AVF+MCT group (n=15): The rats were given a single subcutaneous crotaline(50 mg/kg) after the AVF operation to make the model of PAH; ③AVF+MCT+MSCs group: 5×106 MSCs labeled with Hoechst 33342 were injected into the rats through tail vein 4weeks after the shunting operation; ④AVF+MCT+DMEM/F12 group: The rats were injected respectively a single subcutaneous cell culture medium 4weeks after the shunting operation.The mean pulmonary arterial pressure (mPAP), right ventricle index (RVHI) and the microstructure and remodeling changes of small pulmonary vessels were determined 4 weeks after the MSCs transplantation. RESULTS: Compared with the normal control group,the PAH SD rat model was successfully established after 4 weeks of the AVF+MCT method. Eight weeks after AVF+MCT, mean pulmonary arterial pressure (mPAP) and right ventricle index (RVHI) were significantly enhanced, and pulmonary artery tunica media and right ventriculus wall significantly thickened. The mPAP, RV/(LV+S), MT% and MA% decreased significantly in transplantation group compared to AVF+MCT group(P<001). The mortality rate of PAH rats decreased from 667% to 133%. Fluorescence microscope showed that MSCs labeled with Hoechst 33342 were permanently implanted in the tunica intima of the lung. CONCLUSION: MSCs transplantation can significantly reduce the pressure of pulmonary artery, alleviate the pulmonary arterial remodeling, and lower the mortality rate of PAH rats.

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备注/Memo

备注/Memo:
收稿日期：2013-01-24.
基金项目：第四军医大学西京医院学科助推计划资金资助（XUZT09M15）
通讯作者：孙新，副教授，从事肺动脉高压研究Email:sunxin6@fmmu.edu.cn 作者介绍：石曌玲，硕士生Email:szl0126@sina.com
更新日期/Last Update: 2013-07-16