内皮祖细胞经缓激肽预适应后移植对 急性心肌梗死的治疗作用

目的：观察内皮祖细胞（EPCs）经缓激肽预适应后移植对急性心肌梗死的治疗作用。方法：（1）体外实验：分离培养人脐带血EPCs，分为EPCs组和缓激肽预适应EPCs组，比较两组细胞增殖、凋亡及细胞培养上清液中血管内皮生长因子（VEGF）的含量。（2）体内实验：取BALB/c nude雄性裸鼠32只，随机分为模型对照组、假手术组、单纯EPCs治疗组和缓激肽预适应EPCs治疗组，比较各组小鼠的心肌梗死面积和心肌新生血管密度。结果：（1）缓激肽预适应EPCs组的细胞增殖能力（A490为0.342±0.050）显著高于EPCs组（0.285±0.060），Hoechst阳性细胞比［（31.39±2.28）%］显著低于EPCs组［（35.23±2.65）%］，细胞培养上清液中VEGF含量［（118.76±17.12）pg/mL］显著高于EPCs组［（102.38±15.27） pg/mL］，差异均具有统计学意义（P<0.05）。（2）缓激肽预适应EPCs治疗组小鼠的心肌梗死面积［（25.17±2.42）%］显著低于单纯EPCs治疗组［（32.94±3.64）%］，而心肌微血管密度（54.82±4.79）/HPF（400×）明显高于单纯EPCs组（42.75±3.45），差异均具有统计学意义（P<0.05）。结论：缓激肽预处理能明显促进EPCs增殖，降低细胞凋亡，缓激肽预适应EPCs移植能明显减少小鼠心肌梗死面积并促进心肌血管的新生。

The therapeutical effect of EPCs transplantation after bradykinin preconditioning on the treatment of acute myocardial infarction

Objective: To observe the therapeutical effect of EPCs transplantation after bradykinin(BK) preconditioning effect on the treatment of acute myocardial infarction. Methods: (1)In vitro experiment: Human umbilical cord blood endothelial progenitor cells were isolated and cultured, and then divided into the EPCs group and the BK preconditioning EPCs group. The cell proliferation, apoptosis and the content of vascular endothelial growth factor(VEGF) in cell culture supernatant were compared between the two groups. (2)In vivo experiment: 32 BALB/c nude mice were randomly divided into the model control group, the sham operation group, the EPCs treatment group only and the BK preconditioning EPCs treatment group. The differences of myocardial infarction area and myocardial neovascularization density between the groups were compared. Results: (1)The proliferation capacity of endothelial progenitor cells in the BK preconditioning EPCs group (A490 was 0.342±0.050) was significantly higher than that of EPCs group (0.285±0.06), Hoechst positive cell ratio in the BK preconditioning EPCs group (31.39±2.28)%] was significantly lower than in the EPCs group (35.23±2.65)%], The VEGF content in the culture supernatant of the BK preconditioning EPCs group (118.76±17.12) pg/mL was significantly higher than that of the EPCs group (102.38±15.27) pg/mL], all the differences were statistically significant(all P<0.05). (2)The myocardial infarct size (25.17±2.42)%] in the BK preconditioning EPCs group was significantly lower than that in the EPCs group (32.94±3.64)%], while the myocardial microvessel density in the BK preconditioning EPCs group (54.82±4.79) was significantly higher than that in the EPCs group (42.75±3.45), both the difference were statistically significant(both P<0.05). Conclusion: Bradykinin preconditioning could promote the proliferation of EPCs and apoptosis of cardiac muscle cells, BK preconditioning with EPCs can significantly reduce myocardial infarct size and promote angiogenesis.