中国医科大学附属第一临床医院循环内科,中国医科大学附属第一临床医院老年病科,中国医科大学附属第一临床医院循环内科
Department of Cardiology,The First Affiliated Hospital,China Medical University,Department of Gerontology and Geriatrics,The First Affiliated Hospital,China Medical University,Department of Cardiology,The First Affiliated Hospital,China Medical University
通过对心肌胶原纤维、微血管生成、血管内皮生长因子(VEGF)及其受体表达的研究,探讨骨髓基质干细胞(BMSSCs)心肌内移植对扩张型心肌病心衰大鼠心功能的保护机制.应用阿霉素注射法建立扩张型心肌病心衰大鼠模型,成功建模后移植4', 6-二乙酰基-2-苯基吲哚(DAPI)标记的BMSSCs.分别于术后1、2、3、4周进行血流动力学检测,利用免疫组化、RT-PCR技术分析心肌胶原纤维、血管内皮生长因子(VEGF)及其受体Flt-1、Flk-1表达的改变,以及微血管密度.结果显示,移植细胞于术后4周通过免疫荧光可检测到存活.于术后2周开始,移植组心功能较对照组改善,表现为移植组收缩压(LVSP)、左心室内压最大上升或下降速率(?dp/dt)较对照组显著升高,舒张压(LVDP)显著下降,P < 0.05.移植组心肌胶原纤维沉积减少,光密度值比较P < 0.05.移植组VEGF、Flt-1、Flk-1表达较同期对照组增加,并张且与其受体达峰时间不同步.4周时移植组微血管密度明显高于对照组.上述结果表明,BMSSCs移植后可通过上调受体内VEGF、Flt-1、Flk-1的表达,促进血管新生,减少胶原纤维沉积,从而改善受体心脏的功能.
Bone marrow stroma stem cells (BMSSCs) have shown promising future in repairing injured myocardium. However, few studies have explored the potential mechanism of BMSSCs transplantation for dilated cardiomyopathy (DCM). In this study we aimed to examine whether BMSSCs transplantation can improves the cardiac function of dilated cardiomyopathy of rats and investigate the possible mechanism of BMSSCs transplantation improving the cardiac function of dilated cardiomyopathy according to investigate the collagen fiber deposition, capillary density, VEGF and its receptor expression. Global heart failure in Wistar rats was induced by means of adriamycin administration, after labeled with DAPI, BMSSCs were transplanted into the myocardium of rats which were divided into transplantation group and control group. At 1w, 2w, 3w, 4w after transplantation, heart function was measured by hemodynamic, the deposition of collagen fiber, expressions of VEGF and its receptor and capillary density were checked by immunochemistry and RT-PCR. Immunofluorescence microscopy revealed that the transplanted BMSSCs were visible at four weeks after transplantation. Compared with the control group, the transplantation group had a significantly higher maximum rate of rise and decline (?dp/dt) of left ventricular pressure and left ventricular systolic pressure (P < 0.05), as well as a significantly lower rate of left ventricular diastolic pressure (P < 0.05). The deposition of collagen fibers in the myocardium of transplantation group was reduced, according to A value in transplant group is less than control group (P < 0.05). The expression of VEGF and its receptor were significantly higher than those of control group, and the upregulation of VEGF and its receptors was unsynchronized, the capillary density is higher in transplantation group than control group after four weeks. Taken together, our results suggest that BMSSCs transplantation can improve dilated cardiomyopathy's heart function of rats, we found that BMSSCs transplantation prevented the fusion of collagen fibers to some extent, decrease the deposition of collagen fiber and maintained the orderly structural arrangement of myocardial tissue. BMSSCs transplantation can also promote the angiogenesis, in our study we found that capillary density increased, BMSSCs transplantation not only upregulated the expression of VEGF, but also upregulated the expression of VEGF receptors. Unsynchronized upregulation of VEGF and its receptors was observed which may promote angiogenesis continuously and steadily.
周瀛,白小涓,王勃.骨髓基质干细胞移植对扩张型心肌病心衰大鼠心功能改善作用机制的研究[J].生物化学与生物物理进展,2013,40(9):859-865
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