葡萄糖溶液缓解急性高原反应的细胞模型探索

A cellular model on glucose solution alleviating the acute high-altitude sickness

目的:研究高浓度葡萄糖干预对血管内皮细胞氧化应激损伤以及炎症反应有何作用。方法:分别用过氧化氢(H2O2)和脂多糖(LPS)处理细胞,模拟细胞的急性氧化应激损伤和炎症反应,分别用高浓度葡萄糖、皮质醇或者二者联合的培养液对细胞进行不同时间和方案的预处理,主要观察高浓度葡萄糖对血管内皮细胞氧化应激损伤的作用模式以及炎症致血管内皮细胞分泌血管内皮生长因子(VEGF)的影响。结果:高浓度葡糖的作用可明显减轻H2O2对HUVEC的损伤,皮质醇(50μM)本身对HUVEC的影响不大,但是将高浓度葡萄糖和皮质醇联合在一起作用于血管内皮细胞时,高糖对细胞的保护作用显著减弱了。高浓度葡萄糖显著上调血管内皮细胞内BETA-ARRESTIN1蛋白的表达,但皮质醇却部分抑制了BETA-ARRESTIN1的上调。LPS刺激血管内皮细胞分泌VEGF,但高浓度葡萄糖存在时这种作用被抑制。结论:一定时间内高浓度葡萄糖的干预可以明显减轻氧化应激所致的血管内皮细胞损伤,皮质醇同时存在时效果削弱;高浓度葡萄糖还可以抑制LPS诱导的血管内皮细胞分泌VEGF。这些细胞实验结果从新的视角部分解释了,为什么紧张焦虑会(皮质醇水平增加)加重急性高原反应,而实际生活中大量服用葡萄糖溶液可以明显缓解初到高原时的急性高原反应症状。

The study is to investigate the effect of high concentration glucose on human umbilical vein endothelial cells(HUVECs)treating with hydrogen peroxide(H2O2)mimicking hypoxia-induced oxidative stress cell injury and/or with LPS inducing inflammatory reactions.We found that shortly pre-treated(4 hours)with high concentration of glucose significantly reduced the cell damage of H2O2 to HUVECs.Cortisol(50μM)has little effect on HUVECs,yet when the high concentration of glucose combined with cortisol,the protective effects of the high concentration of glucose were significantly reduced.Also there was a significant difference between high concentration of glucose and the combination with cortisol on the expression of beta-arrestin 1 in HUVECs.High concentration of glucose up-regulated the expression of beta-arrestin1,but it was significantly inhibited when together with cortisol.LPS stimulated HUVECs to secrete VEGF,while this effect was inhibited by high concentration of glucose.So we make a conclusion that,not a long time treated with high concentration glucose on HUVECs could protect cells from oxidative stress induced injury,while this protective effect was weakened in the presence of cortisol.Moreover,high concentration of glucose might also inhibit the secretion of the VEGF by the HUVECs induced of theLPS.These cellular results provided a new perspective on why stress and anxiety(increased cortisol levels)might aggravate acute altitude sickness,whereas in practice,high doses of glucose solution might significantly alleviate symptoms of an acute high-altitude sickness.