经冠状动脉自体骨髓单个核细胞移植对阿霉素心肌病兔心功能的影响  

Effects of autologous intracoronary bone marrow mononuclear cell transplantation on cardiac function in adriamycin-induced cardiomyopathic rabbits

作　　者：金波[1] 施海明[1] 李剑[1] 李勇[1] 罗心平[1] 王逸平[2] 孙伟康[2] 朱军[1] 黄成磊[1] 沈伟[1] 

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

出　　处：《上海医学》2008年第5期328-331,F0004,共5页Shanghai Medical Journal

基　　金：上海市卫生局科技发展基金(054065)

摘　　要：目的建立经冠状动脉输注自体骨髓单个核细胞(BMNNCs)治疗阿霉素诱导的扩张型心肌病(DCM)新西兰兔的移植模型,评价BMMNCs移植对心肌间质重塑的影响,初步探讨移植后心肌间质重塑与心功能改善的内在联系。方法经耳缘静脉注射盐酸阿霉素建立新西兰兔DCM模型,将存活的DCM模型兔随机分为冠状动脉移植亚组(10只,经冠状动脉输注自体BMNNCs)和对照亚组(10只,假手术)。半定量分析左心室心肌胶原容积分数(CVF)、基质金属蛋白酶(MMP)-2和MMP-3,以评价心肌间质重塑;测定血流动力学指标和血清脑钠素(BNP),以评价心功能的改变。结果BMMNCs移植术4周后,冠状动脉移植亚组的心肌组织MMP-2和MMP-3表达呈下降趋势(P值均<0.01);左心室CVF的增幅为(0.97±1.94)%,显著低于对照亚组的(11.58±2.82)%(P<0.05)。冠状动脉移植亚组移植后8周的血清BNP为(172.16±15.28)μg/L,显著高于移植后14周的(128.46±10.02)μg/L(P<0.01)。结论经冠状动脉的自体BMMNCs移植,可能通过抑制MMPs的应激性改变而延缓心肌间质重塑中胶原代谢进程,有助于改善新西兰兔DCM模型的心功能。Objective To establish a new animal model of autologous intracoronary bone marrow mononuclear cells（BMMNCs） transplantation in adriamycin-induced dilated cardiomyopathic（DCM） rabbits and evaluate the cardiac matrix remodeling after transplantation,in an attempt to explore the relationship between cardiac remodeling and the improvement of cardiac function. Methods Adriamycin was injected through ear-bordcr vein to produce DCM model with male New Zealand rabbits. Twenty survived DCM rabbits were equally randomized into intracoronary transplant group and control group. Autologous BMMNCs were infused into the left coronary artery in the intracoronary transplant group through plastic 4F catheter. The collagen volume fraction（CVF）, matrix metalloproteinase（MMP）-2 and MMP-3 in the left ventricular myocardium were semi-quantitative determined to evaluate the cardiac matrix remodeling; indices of hemodynamics and rabbit serum brain natriuretic peptide （BNP） concentration were measured for evaluation of the cardiac function. Results Four weeks later, BMMNCs transplantation significantly improved the cardiac function and decreased the expression of MMP-2 and MMP-3 in the myocardium; the CVF increased by （0.97±1.94） % in the transplantation group and by （11.58±2.82） % in the control group. The serum BNP level decreased from （172. 16± 15.28） μg/L to （128. 46 ± 10.02） μg/L in the transplant group （P 〈 0. 01 ）. Conclusion Autologous intracoronary transplantation of BMMNCs in DCM rabbits can delay the progress of collagen metabolism during cardiac matrix remodeling; which might be related to the inhibition of stress-associated MMPs changes and delay of the collagen metabolism during cardiac matrix remode-ling, subsequently resulting in the improvement of cardiac function. （Shanghai Med J, 2008, 31： 328-331）

关 键 词：扩张型心肌病 间质重塑 基质金属蛋白酶 新西兰兔 细胞移植 

分 类 号：R542.2[医药卫生—心血管疾病]