γ- 分泌酶抑制剂对糖基化终产物作用下心肌微血管 内皮细胞的影响

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。

The Effects of DAPT Under Advanced Glycation End Products on Microvascular Endothelial Cells

Objective:To investigate the effect of DAPT under the advanced glycation end products(AGEs) on proliferation,migration,angiogenesis and lumen formation of cardiac microvascular endothelial cells(CMECs).Methods: CMECs isolated from the hearts of adult rats were exposed to hypoxia(94%N2,5%CO2,1%O2).The cells were incubated with different concentrations(in μmol/L:0,0.25,0.5,1.0,5.0,10.0) of DAPT for 24h,or incubated with DAPT(5 μ mol/L) for 24h,48h,72h,96h and 120h.The cell viability of CMECs was measured by MTT method and migration ability of CMECs was detected by Tranwell method.Capillary lumen formation test was applied to detect the angiogenesis.Results: The viability of CMECs depressed with DAPT incubation.Conclusion: DAPT can interrupt the transduction of Notch signaling pathway in cardiac microvascular endothelial cells(CMECs) and inhibit the viability of the cells and increase their apoptosis.