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山东大学学报(医学版) ›› 2011, Vol. 49 ›› Issue (8): 31-.

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骨髓间充质干细胞移植治疗实验性大鼠肺动脉高压损伤的作用

张兆华1,王一彪1,栾云2,苏宏1,马宇1,林梅1,孙若鹏3   

  1. 山东大学 1.第二医院儿内科, 济南 250033; 2.第二医院中心实验室, 济南 250033; 3.齐鲁医院儿科, 济南 250012
  • 收稿日期:2011-04-18 出版日期:2011-08-10 发布日期:2011-08-10
  • 通讯作者: 孙若鹏(1949- ),男,教授,博士生导师,主要从事小儿神经系统疾病的研究。 E-mail:ruopengsun@yahoo.com.cn
  • 作者简介:张兆华(1972- ),女,博士研究生,主治医师,主要从事儿科心血管疾病的研究。 E-mail:zhaohuaz1972@126.com

Effect of mesenchymal stem cells implantation on experimental  impairment caused by pulmonary arterial hypertension in rats

ZHANG Zhaohua1, WANG Yibiao1, LUAN Yun2, SU Hong1, MA Yu1, LIN Mei1, SUN Ruopeng3   

  1. 1. Department of Pediatrics, the Second Hospital of Shandong University, Jinan 250033,China;
    2. Central Laboratory, the Second Hospital of Shandong University, Jinan 250033, China;
    3. Department of Pediatrics, Qilu Hospital of Shandong University, Jinan 250012, China
  • Received:2011-04-18 Online:2011-08-10 Published:2011-08-10

摘要:

目的      探讨骨髓间充质干细胞(MSCs)移植治疗肺动脉高压(PAH)致右心室损伤的作用效果及其机制,观察MSCs移植后存活及转化情况。方法     取SD大鼠骨髓,经贴壁筛选法体外培养并纯化MSCs,CMDiI荧光染料标记后备用。将实验动物随机分为MSCs移植治疗组(MSCs组)、肺动脉高压模型组(PAH组)和生理盐水阴性对照组(对照组),每组10只。MSCs组和PAH组大鼠皮下注射野百合碱(MCT)建立肺动脉高压模型,对照组皮下注射等量0.9%生理盐水代替MCT;1周后MSCs组大鼠经舌下静脉注射MSCs细胞悬液1mL,对照组及PAH组注射等量低糖DMEM液。移植3周后荧光显微镜下观察MSCs体内存活及转化情况,并对右心室(RV)肥厚和右心室收缩压(RVSP)升高情况进行评价。结果    MSCs在大鼠体内能存活至少3周,荧光显微镜可见MSCs转化为血管平滑肌细胞,与PAH组相比,MSCs组RVSP及RV质量与体质量比值明显降低。结论     静脉移植MSCs可明显减轻甚至逆转MCT诱导的肺动脉高压的进程,改善心功能及血流动力学指标,其机制可能是通过旁分泌作用实现的。

关键词: 骨髓间充质干细胞;移植;肺动脉高压;右心室损伤

Abstract:

Objective     To investigate the therapeutic mechanism of bone marrow mesenchymal stem cells (MSCs) transp1antation on the model of pulmonary arterial hypertension (PAH) and observe the survived and transformed MSCs in PAH after 3weeks. Methods      MSCs were isolated, cultured from bone marrow of SD rats, and stained with CMDiI fluoresence dye in vitro. The rats were randomly divided into three groups (n=10): MSCs group, nontreatment group (PAH group) and control group. PAH model was induced by subcutaneous injection of MCT in MSCs and PAH groups, the rats of control group were injected with normal saline instead of MCT. One week after the MCT administration, MSCs were injected through ranine vein into the rats in MSCs group. At the same time, the rats in PAH and control groups were injected with low-glucose DMEM. Three weeks after the injection, the bone marrow-derived mesenchymal stem cell survival and transformation were observed by immunofluorescence microscopy. Right ventricular (RV) hypertrophy and the elevation of RV systolic pressure (RVSP) were evaluated. Result     Immunofluorescence and histochemical results confirmed that transplanted MSCs were still alive after 3 weeks, and parts of them appeared to differentiate into pulmonary vascular endothelial cells. Compared with PAH group, RV hypertrophy and RVSP weresignificantly decreased. Conclusion      Intravenous implantation of MSCs can significantly reduce or even reverse the progression of MCTinduced pulmonary arterial hypertension to improve the cardiac function and hemodynamics. The mechanism may be attributed to the paracrine effects.

Key words: Mesenchymal stem cells; Transplantation; Pulmonary arterial hypertension; Right ventricular impairments

中图分类号: 

  • R725.4
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