High glucose concentration inhibits migration of rat cranial neural crest cells in vitro
High glucose concentration inhibits migration of rat cranial neural crest cells in vitro
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DOI：
10.1007/bf00400671
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发表时间：
1996-04-01
期刊：
影响因子：
8.2
通讯作者：
Eriksson, UJ
中科院分区：
文献类型：
--
作者：
Suzuki, N;Svensson, K;Eriksson, UJ
颅神经嵴细胞产生大部分面部结构，因此这些细胞的发育紊乱可能导致影响头部和面部的先天性畸形。本实验研究了体外培养48 h的颅神经嵴细胞在高浓度葡萄糖作用下的迁移和发育。在妊娠第9天，从正常和糖尿病大鼠的胚胎中取出迁移前颅神经嵴细胞。在10 mmol/l葡萄糖中24 h后，将细胞暴露于10、30或50 mmol/l葡萄糖浓度下另外24 h。在24 h和48 h时在相差显微镜下对培养物拍照，以评价细胞形态、细胞数量和细胞迁移。与10 mmol/l葡萄糖培养的细胞相比，暴露于50 mmol/l葡萄糖减少了神经嵴细胞的总数，其平均迁移距离和迁移面积扩展。为了研究抗氧化剂的作用，在添加N-乙酰半胱氨酸（NAG）或超氧化物歧化酶（SOD）后研究了高糖培养物。NAC的加入减弱了高糖的抑制作用，而SOD对细胞发育没有任何改善作用。与正常细胞相比，糖尿病大鼠胚胎的神经嵴细胞培养物在所有葡萄糖浓度下均显示细胞迁移减少。此外，糖尿病大鼠胚胎的细胞在基础10 mmol/l葡萄糖浓度下培养后迁移面积扩张减少，表明母体糖尿病永久性地影响了迁移前颅神经嵴细胞的未来发育。这些研究结果表明，高浓度的葡萄糖抑制颅神经嵴发育在体外，抗氧化剂治疗可能会减少这种抑制。自由基氧可能参与畸形的诱导，因此抗氧化剂可能在未来尝试阻断糖尿病妊娠的致畸作用中发挥作用。
Cranial neural crest cells give rise to a large part of the facial structures, and disturbed development of these cells may therefore cause congenital malformations affecting the head and face. We studied the effects of increased glucose concentration on the migration and development of cranial neural crest cells, maintained in vitro for 48 h. Pre-migratory cranial neural crest cells were removed from embryos of normal and diabetic rats on gestational day 9. After 24 h in 10 mmol/l glucose the cells were exposed to glucose concentrations of 10, 30, or 50 mmol/l for another 24 h. The cultures were photographed at 24 h and 48 h in a phase-contrast microscope to evaluate cell morphology, cell number, and cell migration. Exposure to 50 mmol/l glucose reduced the total number of neural crest cells, their mean migratory distance and migratory area expansion compared to cells cultured in 10 mmol/l glucose. To investigate the effect of antioxidant agents, high glucose cultures were studied after addition of N-acetylcysteine (NAG), or superoxide dismutase (SOD). Addition of NAC diminished the inhibitory effect of high glucose, whereas SOD did not offer any improvement in cell development. Neural crest cell culture from embryos of diabetic rats showed reduced cell migration in vitro at all glucose concentrations compared to normal cells. In addition, the cells from embryos of diabetic rats showed reduced migratory area expansion after culture in the basal 10 mmol/l glucose concentration, indicating that maternal diabetes permanently influences the future development of premigratory cranial neural crest cells. These findings indicate that high glucose concentration inhibits cranial neural crest development in vitro, and that antioxidant therapy may diminish this inhibition. Free radical oxygen species may be involved in the induction of malformations and antioxidants may therefore have a role in future attempts to block the teratogenic effects of diabetic pregnancy.