自体骨髓单个核细胞移植起搏器诱导心力衰竭犬心功能变化 病理图像分析心脏切片胶原纤维定量的客观价值  

Heart function changes following transplantation of autologous bone marrow mononuclear cells in a canine model of heart failure induced by rapid ventricular pacing:Pathological image analysis of collagen fiber

作　　者：李海嵘[1] 徐爱国[1] 张云强[1] 齐向前[1] 

机构地区：[1]天津医科大学心血管病临床学院泰达国际心血管病医院内二科,天津市300457

出　　处：《中国组织工程研究与临床康复》2010年第1期116-120,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

摘　　要：背景:干细胞再生可修复受损心肌,但目前利用骨髓单个核细胞移植治疗非缺血性心力衰竭的研究相对甚少。目的:探讨自体骨髓单个核细胞心肌移植后,对起搏器诱导的心力衰竭模型犬心功能的影响。方法:细胞移植组、模型对照组犬均通过快速右室心尖部起搏建立心力衰竭模型。造模后,细胞移植组通过心肌直接注射法分多点注入CM-DiI标记的骨髓单个核细胞悬液,模型对照组同法注入等量生理盐水。4周后取材,取心尖、前壁和室间隔心肌,FITC标记心肌肌钙蛋白,观察心肌纤维化程度,测定心肌胶原容积分数,并进行血流动力学检查。结果与结论:细胞移植组可见CM-DiI和FITC双重染色的双阳性的细胞,呈黄色荧光;模型对照组仅可见FITC染色的绿色荧光图像。苏木精-伊红及Masson染色结果示,模型对照组间质中可见炎性细胞浸润,呈显著间质纤维化和心肌细胞纤维化;而细胞移植组未见明显间质炎性细胞浸润,间质无心肌细胞纤维化,提示快速右室心尖部起搏可成功建立犬心力衰竭模型。与模型对照组比较,移植后4周细胞移植组心尖、前壁、室间隔的胶原容积分数均明显降低(P<0.05),射血分数明显升高(P<0.05),左室舒张末期内径及左室收缩末内径均无明显变化(P>0.05)。说明自体骨髓单个核细胞在心力衰竭犬心肌中可增殖分化为心肌样细胞,并改善心功能,其机制可能与抑制心力衰竭心肌纤维化进程有关。BACKGROUND： Stem cell regeneration can repair injured myocardium. However, bone marrow mononuclear cells （BM-MNCs） transplantation for non-ischemic heart failure remains poorly understood. OBJECTIVE： To investigate effect of transplantation of autologous BM-MNCs on cardiac function in canine model of heart failure by rapid ventricular pacing. METHODS： Implantation and model control groups were subjected to model establishment of heart failure by rapid pacing of apex of right ventricle, and respectively injected with CM-DiI-labeled BM-MNCs and normal saline into myocardium. After 4 weeks, all dogs were sacrificed, and specimens of myocardium were collected from the apex, anterior wall and interventricular septum. All specimens were labeled by FITC. Myocardial fibrosis conditions of implanted cells were observed, collagen volume fraction was determined, and hemodynamic indexes were measured. RESULTS AND CONCLUSION： BM-MNCs labeled by CM-DiI and FITC were observed in the transplantation group showing yellow fluorescence, while in the control group FITC-labeled green fluorescence was seen. HE and Masson staining showed that inflammatory cell infiltration in interstitial matrix, displaying interstitial fibrosis and myocardial fibrosis in model control group, but no obvious inflammatory cell infiltration or myocardial fibrosis was observed in the transplantation group, indicating a success model establishment of heart failure by rapid ventricular pacing. Compared with model control group, the collagen volume fraction decreased significantly （P 0.05）, ejection fracture remarkably increased （P 0.05）, but left ventricular end-diastolic and end-systolic diameter remained unchanged in the transplantation group （P 0.05）. Autologous BM-MNCs in canine model of heart failure show myocardium-like cells differentiation, and improve heart function, which possibly associate with the ability of inhibiting the myocardial fibrosis.

关 键 词：心力衰竭 移植 纤维化 骨髓单个核细胞 干细胞 

分 类 号：R394.2[医药卫生—医学遗传学]