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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 transplanted model of doxorubicin-induced dilated cardiomyopathy (DCM) in New Zealand white rabbits by transplanting autologous bone marrow mononuclear cells (BMNNCs) into coronary arteries and evaluate the effect of BMMNCs transplantation on myocardial interstitial remodeling. Intermyocardial remodeling and improvement of cardiac function. Methods New Zealand rabbit model of DCM was established by injecting doxorubicin hydrochloride into the ear vein. The surviving DCM model rabbits were randomly divided into two groups: coronary artery transplantation group (10 rats, autologous BMNNCs by coronary artery infusion) and control group (10 rats, Sham surgery). Left ventricular myocardial collagen volume fraction (CVF), matrix metalloproteinase (MMP) -2 and MMP-3 were semi-quantitatively analyzed to evaluate myocardial interstitial remodeling. The hemodynamics and serum brain natriuretic peptide (BNP) Evaluation of cardiac function changes. Results After 4 weeks of BMMNCs transplantation, the expression of MMP-2 and MMP-3 in the myocardium in the subgroups of coronary artery transplantation showed a decreasing trend (all P <0.01). The amplitude of CVF in the left ventricle was (0.97 ± 1.94)%, significantly lower (11.58 ± 2.82)% (P <0.05) in the control subgroup. Serum BNP was (172.16 ± 15.28) μg / L at 8 weeks after transplantation in subgroups of coronary artery transplantation, which was significantly higher than that at 14 weeks after transplantation (128.46 ± 10.02 μg / L, P <0.01). Conclusion Transplantation of autologous BMMNCs via coronary artery may delay the process of collagen metabolism in myocardial interstitial remodeling by inhibiting the stress changes of MMPs, which may be helpful to improve the cardiac function of DCM model in New Zealand rabbits.