AGEs诱发大鼠心脏微血管内皮细胞eNOS脱偶联

AGEs induced eNOS uncoupling in cardiac microvascular endothelial cells in rat

目的:观察牛血清白蛋白糖基化终末产物(BSA-AGEs)诱导心脏微血管内皮细胞内一氧化氮(NO)生成与内皮型一氧化氮合酶(eNOS)表达的变化及相关性。方法:体外原代培养大鼠心脏微血管内皮细胞,采用不同梯度浓度的BSA-AGEs(50～200mg/L)分别作用0～24 h,检测NO与超氧阴离子(O2-)、eNOS蛋白表达和四氢生物喋呤(BH4)含量。结果:随着AGEs浓度增加及作用时间的延长,心脏微血管内皮细胞中O2-生成增多,NO生成减少,eNOS蛋白表达增加;BH4生成减少(P<0.05)。结论:BSA-AGEs可以诱发心脏微血管内皮细胞eNOS脱偶联的发生,从而引发以微血管内皮功能障碍。

Objective：To observe the effect of the advanced glycation end products （AGEs） on the eNOS expression in cardiac microvascular endothelial cells. Methods： The cardiac microvascular endothelial cells were cultured in vitro. After treatment of the cells with different doses（50-200 mg/L）o{ AGEs for different times （0-24h）, we determined the NO and 02 generation and eNOS protein expression in all groups. Results： NO generation （90. 53 ± 0.44）μmol/L and BH4 generation（205.00± 2. 89） pg/ml were decreased, and eNOS protein expression（129. 75 ± l. 15） and 02 generation （171. 75±2.31） umol/I, increased with increasing AGEs-dose and treatment time （all P〈I）. 05）. Conclusion：These results demonstrate that AGEs may induce eNOS uncoupling in cardiac microvascular endothelial cells, causing endothelial dysfunction.