脂肪间充质干细胞移植对大鼠心肌缺血再灌注后炎症反应及心脏功能的影响

Effect of adipose-derived mesenchymal stem cell transplantation on inflammatory response and ventricular remodeling after myocardial ischemia reperfusion

  • 摘要: 目的 观察脂肪间充质干细胞(adipose-derived mesenchymal stem cells,ADSCs)移植对心肌缺血再灌注后炎症反应及心脏功能的影响。 方法 5只SD大鼠(5 ~ 7d)体外分离、培养、鉴定ADSCs。60只SD大鼠(250 g左右)随机分为假手术组(n=20)、模型对照组(n=20)和ADSCs治疗组(n=20),采用40 min短暂结扎冠状动脉前降支建立心肌缺血再灌注模型。48 h后TTC-偶氮蓝染色观察梗死面积,HE染色观察炎症反应,流式细胞学分析免疫细胞比例;28d后心脏超声检测左心室短轴缩短率(fraction shortening,FS)、射血分数(ejection fraction,EF),血流动力学检测左心室收缩压、左心室舒张末压和最大变化率(+dp/dtmax)、最小变化率(-dp/dtmin)。 结果 细胞移植48 h后,与模型对照组相比,ADSCs治疗组心梗区面积和心梗区与危险区的比值显著减小(14.372%±3.482% vs 8.364%±3.47%,33.482%±4.261% vs 16.384%±4.238%,P< 0.05),炎症反应减轻,白细胞数和中性粒细胞比例显著减少(64.25%±2.228% vs 54.65%±1.613%,16.325%±1.506% vs 6.695%±0.671%,P< 0.05),而巨噬细胞比例及M2型巨噬细胞所占比例明显上升(10.525%±0.896% vs 18.5%±0.589%,32.4%±2.407% vs 50%±3.822%,P< 0.05);细胞移植48 h后,与模型对照组相比,ADSCs治疗组FS、EF、+dp/dtmax、-dp/dtmin显著升高(29.617±3.462 vs 40.175±2.447,62.683%±5.392% vs 76.760%±2.709%,1 419.759±228.753 vs 3 458.153±592.408,1 417.008±296.541 vs 3 047.759±763.195,P< 0.05)。 结论 ADSCs移植可减轻大鼠心肌缺血再灌注后炎症反应,减小心梗面积,延缓心室重构,改善心脏功能。

     

    Abstract: Objective To observe the effect of adipose-derived mesenchymal stem cells (ADSCs) transplantation on inflammatory reaction and cardiac function after myocardial ischemia reperfusion. Methods The ADSCs in SD rats were isolated, cultured, and identified. Sixty SD rats (250 g) were randomlydivided into sham, control and ADSCs group, and myocardial ischemia reperfusion models were established by transient ligation of the left anteriordescending coronary artery for 40 min. TTC/Evans blue staining for infarct size, HE staining for inflammatory reaction and Flow cymetory analysis for immune cell proportion were performed at 48 hours after operation. Left ventricular fractional shortening (FS) and ejection fraction (EF) weredetected by echocardiography, and left ventricular systolic pressure, left ventricular enddiastolic pressure and +dp/dtmaxand -dp/dtminweredetected by hemodynamics at 28days after operation. Results Compared with control group, infarct size and infarct size/AARdecreased significantly (14.372%±3.482%) vs (8.364%±3.47%), (33.482%±4.261%) vs (16.384%±4.238%), P< 0.05, inflammation response was relieved, ratios of leukocytes and neutrophilsdecreased (64.25%±2.228%) vs (54.65%±1.613%), (16.325%±1.506%) vs (6.695%±0.671%), P< 0.05, while ratios of macrophages and M2 macrophages increased in ADSCs group at 48 hours after operation (10.525%±0.896%) vs (18.5%±0.589%), (32.4%±2.407%) vs (50%±3.822%), P< 0.05; Compared with control group, FS, EF, +dp/dtmaxand -dp/dtminimproved in ADSCs group at 28days after operation (29.617±3.462) vs (40.175±2.447), (62.683%±5.392%) vs (76.760%±2.709%), (1 419.759±228.753) vs (3 458.153±592.408), (1 417.008±296.541) vs (3 047.759±763.195), P< 0.05. Conclusion ADSCs transplantation reduces cardiac inflammation, decreases infarct size, thusdelays ventricular remodeling and improves cardiac function in rats after myocardial ischemia reperfusion.

     

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