经冠状动脉内自体骨髓干细胞移植对不同基础心功能影响及其机制探讨

Effects of Bone Marrow Cell Transplantation by Coronary Delivery on the Different Basic Cardiac Function Degrees and Its Mechanisms

目的:通过建立小型猪心肌梗死模型,引起不同程度心功能变化,进行冠状动脉内自体骨髓细胞移植,探讨骨髓干细胞移植除与血管新生相关外,是否与动物基础心功能水平和侧枝循环变化相关。方法:结扎小型猪不同部位左前降支血管,造成不同程度心功能变化,2周后经冠状动脉内移植骨髓单个核细胞或盐水。冠脉造影评估侧枝循环情况;左室造影检测左室射血分数(LVEF)变化;组织学检测新生血管数量。结果:移植后4周,注射PBS组动物LVEF呈进行性下降,各降低15．5％和14．2％(P<0．01);低EF +BMT组较移植前增加14．4％(P<0．01),而高EF+BMT组较移植前仅增加5．6％(P>0．05)。冠脉造影显示,骨髓干移植组侧枝循环数量较移植前增加,但无显著差异(P>0．05),注射PBS组也无显著变化(P>0．5)。碱性磷酸酶法显示,骨髓干移植组新生血管密度较注射PBS组增加(P<0．01),而低EF组移植骨髓干细胞引起的新生血管密度较高EF组增加63％(P<0．01)。相关分析显示,骨髓干细胞移植引起低EF组的心功能增加幅度与新生血管和基础心功能呈良好正相关(P<0．05),与侧枝循环级别增加无明显相关性(P>0．05)。结论:经冠状动脉内自体骨髓细胞移植更有利于低基础水平心脏功能恢复,其作用机制与血管新生和基础心功能水平密切相关。

Objective.. To investigate whether BMT causing cardiac function improvement was related to the baseline cardiac function and coronary circulation in addition to angiogenesis. Methods： Different degree of cardiac dysfunction was induced in swines by different segment ligation of left anterior descending artery. Two weeks later, 1 × 10^8 bone marrow-mononuclear cells or salt （PBS） were coronarily injected into the ischemic zone. Coronary angiography （CAG） and left ventriculography （LVG） were performed to evaluate coronary circulation and left ventricular ejection fraction （LVEF）. Angiogenesis count was examined by histology. Results： four weeks post-transplantation, LVG showed that LVEF were increased in both BMT groups and the greater improvements were seen in the low LVEF＋BMT group （P〈 0.01 ）, whereas LVEF showed deterioration in both PBS groups. CAG revealed that BMT caused no significant coronary circulation increase （P〉0. 05）. Alkaline phosphatase staining showed the angiogenesis counts in both BMT groups were significantly greater than those in both PBS groups （P〈0. 01 ）, and the angiogenesis counts in the low LVEF＋BMT group was 63 % greater than there in the high LVEF＋ BMT group, The cardiac function improvement extent caused by BMT in the low LVEF group were positively correlative with angiogenesis count and the baseline cardiac function （P〈0. 05）, but not with coronary circulation （P〉0. 05）. Condusion：These data suggest that coronarily transplantation of bone marrow stem cells more benefit for cardiac function recovery at the low level, which might be due to angiogenesis and the basic cardiac function levd.