经冠状动脉自体骨髓单个核细胞移植对扩张型心肌病兔心肌间质重塑的影响  

Effects of autologous intracoronary bone marrow mononuclear cell transplantation on cardiac matrix remodeling in rabbit models of dilated cardiomyopathy

作　　者：倪唤春[1] 金波[1] 施海明[1] 罗心平[1] 王逸平[2] 孙伟康[2] 朱军[1] 李剑[1] 

机构地区：[1]复旦大学附属华山医院心内科,上海市200040 [2]中科院上海药物研究所,上海市201203

出　　处：《中国组织工程研究与临床康复》2008年第51期10020-10024,共5页Journal of Clinical Rehabilitative Tissue Engineering Research

基　　金：上海市卫生局科技发展基金(054065)~~

摘　　要：背景:骨髓单个核细胞为一组多潜能干细胞的混合体,在原发性扩张型心肌病领域的应用尚处于起步阶段。目的:评价经冠状动脉移植自体骨髓单个核细胞对阿霉素诱导的扩张型心肌病模型兔心肌间质重塑的影响。设计、时间及地点:细胞学体外观察,于2006-10/2007-06在复旦大学附属华山医院心血管研究室完成。材料:普通级3月龄雄性新西兰兔30只,由上海中医药大学实验动物中心提供。阿霉素为深圳万乐药业股份有限公司产品,批号0602E1。方法:30只兔均经耳缘静脉注射盐酸阿霉素建立扩张型心肌病模型,造模后存活兔取10只用于模型观察,剩余20只随机分为移植组、对照组,10只/组。移植组兔抽取髂骨骨髓,采用密度梯度离心法分离自体骨髓单个核细胞,于造模2周后经塑性的4F造影导管模拟临床冠状动脉内输注骨髓单个核细胞悬液2mL。对照组兔同样接受骨髓液采集以平衡手术操作创伤对实验结果的影响,完成选择性左冠状动脉造影后,经造影导管注射2mL生理盐水。主要观察指标:通过RT-PCR半定量检测心肌胶原容积分数、基质金属蛋白酶1,3mRNA的表达评价心肌间质重塑,通过血流动力学指标和血清脑钠素浓度评价心功能的变化。结果:移植组脱落2只,对照组脱落1只。细胞移植4周后与对照组比较,移植组胶原纤维增生进程延缓,心肌胶原容积分数显著降低(P<0.01),基质金属蛋白酶1,3mRNA的表达呈下降趋势(t=4.45,P<0.01),左心室收缩压、压力变化速率最大值均显著升高,左心室舒张末压显著下降(t=9.12,P<0.01),血清脑钠素浓度明显降低(t=6.05,P<0.05)。结论:经冠状动脉移植自体骨髓单个核细胞,可能通过抑制基质金属蛋白酶的应激性改变而延缓心肌间质重塑中胶原代谢进程,有助于改善扩张型心肌病模型兔的心功能。BACKGROUND： Bone marrow mononuclear cells containing a group of multipotential stem cells have been explored as vehicles for cell therapy replacing damaged myocardium of dilated cardiomyopathy （DCM）. OBJECTIVE： To evaluate effects of autologous intracoronary bone marrow mononnclear cell transplantation on cardiac matrix remodeling in adriamycin-induced dilated cardiomyopathy rabbit models. DESIGN, TIME AND SETTING： The cytology in vitro observation experiment was performed at the Department of Cardiology, Huashan Hospital, Fudan University from October 2006 to June 2007. MATERIALS： Thirty 3-months male New Zealand rabbits were supplied by Animal Experimental Center, Shanghai University of Traditional Chinese Medicine. Adriamycin was purchased from Wanle, China, lot number 0602E1. METHODS： Adriamycin was injected to produce New Zealand rabbit models of dilated cardiomyopathy through ear-border vein. After establishment, ten survival rabbits were used for model observation. The remaining twenty rabbits were randomly divided into a transplantation group and a control group equally. Bone marrow was isolated from the rabbit ilium in the transplantation group. Autolougous bone marrow mononuclear cells were separated from bone marrow by density gradient centrifugation. Bone marrow mononuclear cells （2 mL） were infused into the left coronary artery in transplantation group through plastic 4F catheter which is similar to intracoronary BMMNCs transplantation in clinical trials at 2 weeks after model establishment. Bone marrow was obtained from rabbits in the control group to balance the effect of surgery trauma on outcomes. Following selective visualization of the left coronary artery, 2 mL of saline was infused via the visualization catheter. MAIN OUTCOME MEASURES： Cardiac collagen volume fraction, matrix metalloproteinase-1 （MMP-1） and MMP-3 mRNA expression in the left ventricular myocardium were semi-quantitatively determined by RT-PCR to evaluate cardiac matrix remodeling Indexes of hemodynamics

关 键 词：骨髓单个核细胞 基质金属蛋白酶 间质重塑 扩张型心肌病 

分 类 号：R654.2[医药卫生—外科学] R542.2[医药卫生—临床医学]