摘要
目的探讨骨髓间充质干细胞(M SC s)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M SC s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M SC s,CM-D iI荧光染料标记后备用。将实验动物随机分为M SC s移植治疗组(M SC s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。M SC s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M SC s组大鼠经舌下静脉注射M SC s细胞悬液1mL,对照组及PAH组注射等量低糖DM EM液。移植3周后荧光显微镜下观察M SC s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 M SC s在大鼠体内能存活至少3周,荧光显微镜可见M SC s转化为血管平滑肌细胞,与PAH组相比,M SC s组RVSP及RV质量与体质量比值明显降低。结论静脉移植M SC s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。
Objective To investigate the therapeutic mechanism of bone marrow mesenchymal stem cells (MSCs) transplantation 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) : the MSCs group, the non-treat- ment group (PAH group) and the control group. The PAH model was induced by subcutaneous injection of MCT in MSCs and PAH groups, the rats of the control group were injected with normal saline instead of MCT. One week after MCT administration, MSCs were injected through the ranine vein into rats in the MSCs group. At the same time, 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 elevation of RV systolic pressure (RVSP) were evaluated. Result Immunofluores- cence and histochemical results confirmed that transplanted MSCs were still alive after 3 weeks, and some of them ap- peared to differentiate into pulmonary vascular endothelial cells. Compared with the PAH group, RV hypertrophy andRVSP were significantly decreased. Conclusion Intravenous implantation of MSCs can significantly reduce or even re- verse progression of MCT-induced pulmonary arterial hypertension to improve cardiac function and hemodynamics. The mechanism may be attributed to paracrine effects.
出处
《山东大学学报(医学版)》
CAS
北大核心
2011年第8期31-34,40,共5页
Journal of Shandong University:Health Sciences
关键词
骨髓间充质干细胞
移植
肺动脉高压
右心室损伤
Mesenchymal stem cells
Transplantation
Pulmonary arterial hypertension
Right ventricular impairments