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Effect of stromal cell-derived factor-1 on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction

机译:基质细胞源因子-1对急性心肌梗死大鼠心肌细胞凋亡和心功能恢复的影响

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摘要

The aim of the study was to investigate the effect of stromal cell-derived factor-1 (SDF-1) on myocardial apoptosis and cardiac function recovery in rats with acute myocardial infarction (AMI) and the mechanism of the Toll-like receptor (TLR)-4uclear factor-κB (NF-κB) signaling pathway. A total of 64 healthy male F344 rats were randomly divided into the sham operation, model, SDF-1 intervention and SDF-1 antibody groups, with 16 rats in each group. The method of Olivette was used to establish the AMI model by ligation of the left anterior descending artery. Day 1 after establishing the animal model, the rats in the SDF-1 intervention group were injected with 10 µl recombinant SDF-1 (400 ng/ml) in five regions including the myocardial infarction area and the four surrounding areas. The rats in the model group were injected with 10 µl normal saline including the myocardial infarction area and the four surrounding areas, and those in the SDF-1 antibody group were injected with 1 ml SDF-1 antibody (2 µg/ml). Four rats were sacrificed after 1, 3, 7 and 14 days after the intervention, and the analysis was carried out. TUNEL in situ labeled apoptotic cells were used for cell counting, and immunohistochemical staining was performed to measure vascular density. The animal echocardiographic measurement was for the left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), left ventricular fractional shortening (FS) and ejection fraction (EF) values. The results showed that the number of apoptotic cells in the SDF-1 treatment group was significantly lower than those in the other groups at each time-point. The vessel densities in the 3–14 days were significantly greater than those in other groups. At each time-point, the LVEDd and LVESd values were smaller compared with the model group, but greater than the sham operation group and decreased over time. FS and EF values were higher than those in the model group at each time-point, but less than those of the sham operation group and increased over time. The expression levels of TLR-4 and NF-κB at each time-point were significantly higher than those of the remaining groups (p<0.05). In conclusion, SDF-1 is capable of decreasing the apoptosis of cardiac muscle cells in AMI, promoting angiogenesis and improving cardiac function, which may be associated with the activation of the TLR-4/NF-κB signaling pathway.
机译:本研究的目的是研究基质细胞衍生因子1(SDF-1)对急性心肌梗死(AMI)大鼠心肌细胞凋亡和心功能恢复的影响以及Toll样受体(TLR)的机制)-4 /核因子-κB(NF-κB)信号通路。将64只健康的雄性F344大鼠随机分为假手术组,模型组,SDF-1干预组和SDF-1抗体组,每组16只。通过结扎左前降支动脉,采用Olivette方法建立AMI模型。建立动物模型后的第1天,在SDF-1干预组的大鼠的五个区域(包括心肌梗塞区域和四个周围区域)中注射了10 µl重组SDF-1(400 ng / ml)。给模型组的大鼠注射包括心肌梗塞区和四个周围区域在内的10 µl生理盐水,向SDF-1抗体组的大鼠注射1 ml SDF-1抗体(2 µg / ml)。干预后1、3、7和14天处死四只大鼠,并进行分析。 TUNEL原位标记的凋亡细胞用于细胞计数,并进行免疫组织化学染色以测量血管密度。动物超声心动图测量的是左心室舒张末期直径(LVEDd),左心室收缩末期直径(LVESd),左心室分数缩短(FS)和射血分数(EF)值。结果表明,在每个时间点,SDF-1处理组的凋亡细胞数量均显着低于其他组。 3-14天的血管密度显着高于其他组。在每个时间点,LVEDd和LVESd值均与模型组相比较小,但大于假手术组,并随时间而降低。在每个时间点,FS和EF值均高于模型组,但低于假手术组,且随时间增加。各时间点TLR-4和NF-κB的表达水平明显高于其余各组(p <0.05)。总之,SDF-1能够减少AMI中心肌细胞的凋亡,促进血管生成并改善心脏功能,这可能与TLR-4 /NF-κB信号通路的激活有关。

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