冠状动脉内干细胞灌注对载脂蛋白E基因缺陷小鼠离体心脏血液动力学影响的实验研究

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目的评估冠状动脉内细胞灌注对载脂蛋白(apo)E 基因缺陷小鼠离体心脏血液动力学的影响。方法应用 Langendorff 离体心脏灌注模型,观察 apo E 基因缺陷小鼠心脏接受不同剂量干细胞[低剂量细胞组(1.0×10~6细胞),n=10;高剂量细胞组(2.5×10~6细胞),n=10]灌注时的血液动力学变化。选用 WT 小鼠心脏作为对照[低剂量细胞组(1.0×10~6细胞),n=10;高剂量细胞组(2.5×10~6细胞),n=10],比较各组离体心脏细胞注射后5、15和30 min 时的血液动力学指标(包括心率、左心室最大压力、左心室等容收缩期压力最大变化速率、左心室舒张期压力下降最大变化速率、左心室舒张末压变化,同时观察各组冠状动脉血流及漏出液中细胞含量。结果基础状态下 apo E基因缺陷小鼠离体心脏各项血液动力学指标与 WT 小鼠相似。apo E 基因缺陷小鼠各组及对照高剂量细胞注射组离体心脏在接受细胞灌注后30 min 心率显著减慢,左心室舒张末压明显升高,且左心室等容收缩期压力最大变化速率明显降低(与基础测值比较,P 均<0.01),对照低剂量细胞注射组心率明显下降(P<0.05),其他指标变化不明显(P>0.05)。与对照组 WT 小鼠离体心脏比较,apo E 基因缺陷小鼠离体心脏在细胞灌注后各项血液动力学指标显著变差,高剂量细胞灌注组更为明显(P均<0.01)。细胞灌注后各组冠状动脉流量均明显低于基础状态(P 均<0.01),灌注后30 min apo E基因缺陷小鼠高剂量细胞注射组冠状动脉流量变化最为显著(与其他各组比较 P<0.05)。灌注后30 min,大多数从细胞冠状动静脉循环排出心脏(63.2%~77.0%)。结论经冠状动脉干细胞灌注对离体小鼠心脏血液动力学有不良影响,这一不良影响在使用高剂量细胞灌注及对动脉粥样硬化性心脏应用时更为显著。 Objective To evaluate the effect of intracoronary perfusion on isolated hemodynamics in isolated apolipoprotein (apo) E-deficient mice. Methods The heart of apo E gene-deficient mice was treated with Langendorff perfusion in vitro. Low-dose stem cells (1.0 × 10 6 cells, n = 10) were injected into the heart of apo E-deficient mice, and 2.5 × 10 6 cells ), n = 10] hemodynamic changes during perfusion. The hearts of WT mice were used as control (low dose group (1.0 × 10 6 cells), n = 10; high dose group (2.5 × 10 6 cells), n = 10] At 5, 15 and 30 min after injection, the hemodynamic parameters (including heart rate, left ventricular maximum pressure, left ventricular systolic pressure maximum rate of change, left ventricular diastolic pressure drop maximum rate of change, left ventricular end diastolic pressure changes , And observed the blood flow in the coronary arteries and the contents of leachate in each group.Results The hemodynamic indexes of apoE gene-deficient mice in vitro were similar to WT mice in each group Compared with the high-dose group, the isolated heart of the isolated rat hearts significantly slowed down 30 min after myocardial cell infusion, the left ventricular end-diastolic pressure increased significantly, and the maximum rate of left ventricular systolic pressure decreased significantly (compared with the baseline values, P <0.01), the heart rate of control group was significantly decreased (P <0.05), while the other indexes did not change significantly (P> 0.05) .Compared with the isolated heart of WT mice, the apo E gene-deficient mice Body blood cells after the blood perfusion (P <0.01) .After perfusion, the coronary flow in each group was significantly lower than that in basal state (all P <0.01), and the apo E gene at 30 min after perfusion Coronary flow changes were most significant in high-dose cell-injected mice (P <0.05 compared with other groups), and most of them discharged cardiac cells (63.2% -77.0%) from the coronary arteries after 30 minutes of perfusion. Coronary artery stem cell perfusion has adverse effects on the hemodynamics of isolated mouse hearts, a side effect that is more pronounced with high-dose cell perfusion and with atherosclerotic heart applications.
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