Guo Jun, Sang Yaxiong, Yin Tao, Wang Bo, Yang Wenping, Li Xue, Li Huan, Kang Yan
Department of Critical Care Medicine, West China Hospital;
College of Life Science; State Key Laboratory of Biotherapy and Cancer Center, West China Hospital;
Am J Physiol Endocrinol Metab. 2016 May 1;310(9):E734-43. doi: 10.1152/ajpendo.00444.2015. Epub 2016 Feb 23.
Acute glucose fluctuations (AGF) often cause high mortality among critically ill patients, but the mechanisms induced by AGF are not clear. Recent studies suggest that endothelial dysfunction is a key factor that leads to high mortality among critically ill patients. Our goal is to evaluate the phenomenon and mechanisms of endothelial dysfunction induced by AGF. In this study, the functions of human umbilical vein endothelial cells (HUVECs) were compared after treatment with sustained high glucose (SHG), AGF in two groups (AGF1 fluctuations between 5 and 16 mM and AGF2 fluctuations between 5 and 25 mM), and normal glucose levels as a control group (CTR). The medium of the groups was changed every 4 h. The influence of AGF on wound healing was also tested on C57BL/6 mice. The results show that cell proliferation, angiogenesis, and migration functions were injured in the SHG and both AGF groups. AGF2 group shows the worse condition in vitro. In vivo, the wound healing was delayed after the AGF treatment. Furthermore, the markers of apoptosis and autophagy were analyzed. We observed that the autophagy changed in all treatment groups, but apoptosis showed no change. To get to know the mechanism of dysfunction and autophagy, we performed the microRNA chip assay and real-time PCR and found miR-1273g-3p remarkably changed in AGF2 group. After the mimic and inhibitor of miR-1273g-3p were transfected during the AGF2 treatment, we found that the dysfunction and autophagy were partially enhanced by miR-1273g-3p mimic and reversed by miR-1273g-3p inhibitor in AGF2 group. Thus, we conclude that AGF can induce more dysfunction and autophagy, and miR-1273g-3p is also an important factor that leads to the injury.
急性血糖波动（AGF）常导致危重症患者高死亡率，但其引发的机制尚不清楚。近期研究表明，内皮功能障碍是导致危重症患者高死亡率的关键因素。我们的目标是评估AGF诱导的内皮功能障碍现象及机制。在本研究中，比较了人脐静脉内皮细胞（HUVECs）在持续高糖（SHG）、两组AGF（AGF1波动于5至16 mM之间，AGF2波动于5至25 mM之间）处理以及正常血糖水平作为对照组（CTR）后的功能。每组培养基每4小时更换一次。还在C57BL/6小鼠上测试了AGF对伤口愈合的影响。结果显示，SHG组和两个AGF组的细胞增殖、血管生成和迁移功能均受损。AGF2组在体外表现出更差的情况。在体内，AGF处理后伤口愈合延迟。此外，分析了凋亡和自噬标志物。我们观察到所有处理组的自噬均发生变化，但凋亡无变化。为了解功能障碍和自噬的机制，我们进行了微小RNA芯片分析和实时PCR，发现miR-1273g-3p在AGF2组中显著变化。在AGF2处理期间转染miR-1273g-3p的模拟物和抑制剂后，我们发现AGF2组中miR-1273g-3p模拟物部分增强了功能障碍和自噬，而miR-1273g-3p抑制剂则使其逆转。因此，我们得出结论，AGF可诱导更多功能障碍和自噬，且miR-1273g-3p也是导致损伤的重要因素。
