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目的:探讨Notch信号特异性阻断剂γ-分泌酶抑制剂(DAPT)对AGEs作用下的心肌微血管内皮细胞的增殖、迁移、管样结构的影响。方法:SD大鼠心肌微血管内皮细胞体外分离培养后,以不同浓度DAPT(0.25、0.5、1.0、5.0、10μmol/L)干预200mg/LAGEs作用下的CMECs24h,或者与DAPT(5μmol/L)孵育不同时间(24h、48h、72h、96h、120h),采用MTT比色法检测细胞的增值能力;用Transwell法检测细胞的迁移能力;用毛细血管管样结构形成实验检测DAPT对血管新生的影响。结果:DAPT显著抑制AGEs作用下的心肌微血管内皮细胞的存活,同时浓度越高、时间越长,其抑制效果越明显。结论:DAPT通过阻断Notch信号通路,能抑制AGEs作用下的心肌微血管内皮细胞的增殖及血管新生,促进细胞凋亡。
AIM: To investigate the effects of DAPT, a specific inhibitor of Notch signaling, on the proliferation, migration and tube-like structure of cardiac microvascular endothelial cells under the action of AGEs. Methods: After cultured and isolated from rat cardiac microvascular endothelial cells in vitro, the CMECs were treated with different concentrations of DAPT (0.25, 0.5, 1.0, 5.0 and 10μmol / L) for 24 hours or incubated with DAPT (5μmol / L) Time (24h, 48h, 72h, 96h, 120h). Cell viability was measured by MTT colorimetric assay. Cell migration was assayed by Transwell assay. The effect of DAPT on angiogenesis was assayed by capillary tube-like structure formation assay. Results: DAPT significantly inhibited the survival of myocardial microvascular endothelial cells under the action of AGEs. At the same time, the higher the concentration of DAPT, the longer the inhibitory effect was. Conclusion: DAPT can inhibit the proliferation and angiogenesis of cardiac microvascular endothelial cells under the action of AGEs by blocking the Notch signaling pathway, and promote apoptosis.