Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.
Edaravone protected human brain microvascular endothelial cells from methylglyoxal-induced injury by inhibiting AGEs/RAGE/oxidative stress.
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依达拉奉通过抑制 AGEs/RAGE/氧化应激保护人脑微血管内皮细胞免受甲基乙二醛诱导的损伤
DOI：
10.1371/journal.pone.0076025
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dai H
中科院分区：
文献类型：
--
作者：
Li W;Xu H;Hu Y;He P;Ni Z;Xu H;Zhang Z;Dai H
与年龄匹配的非糖尿病患者相比，糖尿病患者发生脑血管疾病和卒中的风险增加。反应性生理性二羰基化合物甲基乙二醛（MGO）的形成增加似乎与糖尿病血管并发症的发展有关，这是由于其蛋白质糖化和氧化应激效应。依达拉奉是一种新型的自由基清除剂，在动物实验和临床试验中均显示出对缺血性脑卒中的有利作用，但依达拉奉是否对糖尿病脑血管损伤具有保护作用尚不清楚。采用体外培养的人脑微血管内皮细胞（HBMEC），观察依达拉奉对MGO及MGO增强OGD损伤的保护作用。通过MTT法、细胞计数、乳酸脱氢酶（LDH）释放和罗丹明123染色检测细胞损伤程度。Western印迹法检测晚期糖基化终产物（AGEs）形成和晚期糖基化终产物受体（AGEs受体）表达。通过活性氧（ROS）释放来测量细胞氧化应激。MGO处理24 h可显著诱导HBMEC损伤，10-100 µmol/l依达拉奉预处理可抑制该损伤。此外，MGO处理增加了培养的HBMEC中AGEs的积累，表达和ROS的释放，100 µmol/l依达拉奉抑制了这些作用。最后，与仅OGD损伤相比，MGO处理24 h，然后进行3 h OGD损伤显著增强了细胞损伤，100 µmol/l依达拉奉也可保护细胞损伤。因此，依达拉奉保护HBMEC免受MGO和MGO通过抑制AGEs/E2/氧化应激增强OGD诱导的损伤。
Subjects with diabetes experience an increased risk of cerebrovascular disease and stroke compared with nondiabetic age-matched individuals. Increased formation of reactive physiological dicarbonyl compound methylglyoxal (MGO) seems to be implicated in the development of diabetic vascular complication due to its protein glycation and oxidative stress effect. Edaravone, a novel radical scavenger, has been reported to display the advantageous effects on ischemic stroke both in animals and clinical trials; however, little is known about whether edaravone has protective effects on diabetic cerebrovascular injury. Using cultured human brain microvascular endothelial cells (HBMEC), protective effects of edaravone on MGO and MGO enhancing oxygen-glucose deprivation (OGD) induced injury were investigated. Cell injury was measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) formation, cell account, lactate dehydrogenase (LDH) release and Rhodamine 123 staining. Advanced glycation end-products (AGEs) formation and receptor for advanced glycation end-products (RAGE) expression were measured by western blotting. Cellular oxidative stress was measured by reactive oxygen species (ROS) release. Treatment of MGO for 24 h significantly induced HBMEC injury, which was inhibited by pretreatment of edaravone from 10–100 µmol/l. What’s more, treatment of MGO enhanced AGEs accumulation, RAGE expression and ROS release in the cultured HBMEC, which were inhibited by 100 µmol/l edaravone. Finally, treatment of MGO for 24 h and then followed by 3 h OGD insult significantly enhanced cell injury when compared with OGD insult only, which was also protected by 100 µmol/l edaravone. Thus, edaravone protected HBMEC from MGO and MGO enhancing OGD-induced injury by inhibiting AGEs/RAGE/oxidative stress.
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影响因子：
5
作者：
Amemiya, S;Kamiya, T;Katayama, Y
通讯作者：
Katayama, Y
DOI：
10.1016/j.bbrc.2004.06.011
发表时间：
2004-07-30
影响因子：
3.1
作者：
Fukunaga, M;Miyata, S;Kasuga, M
通讯作者：
Kasuga, M
羟基红花黄A保护甲基乙二醛诱导的人脑微血管内皮细胞损伤
影响因子：
2.5
作者：
Li, Wenlu;Liu, Jie;Dai, Haibin
通讯作者：
Dai, Haibin
影响因子：
9.9
作者：
Madden, Jane A.
通讯作者：
Madden, Jane A.
影响因子：
14.9
作者：
Murata-Kamiya, N;Kamiya, H
通讯作者：
Kamiya, H