Ceramide profiles in the brain of rats with diabetes induced by streptozotocin
Ceramide profiles in the brain of rats with diabetes induced by streptozotocin
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DOI：
10.1111/j.1742-4658.2012.08575.x
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发表时间：
2012-06-01
期刊：
影响因子：
5.4
通讯作者：
Sawicka, Diana
中科院分区：
文献类型：
--
作者：
Car, Halina;Zendzian-Piotrowska, Malgorzata;Sawicka, Diana
糖尿病与大脑活动紊乱和认知障碍有关。我们假设神经酰胺可能对糖尿病相关的神经功能障碍起重要作用。在我们的研究中，我们用注射链脲佐菌素（STZ）的大鼠作为严重高血糖的模型。采用气液色谱技术，我们发现糖尿病大鼠脑内神经酰胺含量显著增加，血浆中神经酰胺含量显著降低。丝氨酸棕榈酰基转移酶的抑制剂肉豆蔻素减少了高血糖大脑中神经酰胺的产生，尽管单独注射它会产生神经酰胺上调的矛盾效果。肉豆蔻素对对照组和糖尿病大鼠血浆神经酰胺浓度均无影响。各实验组小鼠脑内神经酰胺饱和脂肪酸水平升高，神经酰胺多不饱和脂肪酸水平下调。神经酰胺单不饱和脂肪酸的浓度保持不变。单个神经酰胺种类的模式根据治疗而改变。我们注意到stz引起的脑神经酰胺C16:0， C18:0和C20:0的增加和神经酰胺C18:2脂肪酸水平的强烈下降。肉豆蔻素可以改变脑神经酰胺模式的一些变化。我们发现总神经酰胺-？-6脂肪酸的变化，神经酰胺-？3个浓度。我们得出结论，神经酰胺可能是糖尿病伴脑功能障碍的重要介质。
Diabetes is associated with disturbances of brain activity and cognitive impairment. We hypothesize that ceramides may constitute an important contribution to diabetes-linked neuro-dysfunction. In our study we used rats injected with streptozotocin (STZ) as a model of severe hyperglycemia. Using the gasliquid chromatography technique we found a significant increase of ceramide content in brains and a decrease in plasma of diabetic rats. The inhibitor of serine palmitoyltransferase, myriocin, reduced ceramide generation in hyperglycemic brains, although injected alone it exerted a paradoxical effect of ceramide upregulation. Myriocin had no impact on ceramide concentration in the plasma of either control or diabetic rats. The level of ceramide saturated fatty acids was elevated whereas the level of ceramide poly-unsaturated fatty acids was downregulated in brains of all experimental groups. The concentration of ceramide mono-unsaturated fatty acids remained unchanged. The pattern of individual ceramide species was altered depending on treatment. We noted an STZ-evoked increase of brain ceramide C16:0, C18:0 and C20:0 and a strong decline in ceramide C18:2 fatty acid levels. Some changes of brain ceramide pattern were modified by myriocin. We found a decreased amount of total ceramide-?-6 fatty acids in STZ-treated rat brains and no changes in ceramide-?-3 concentration. We conclude that ceramides may be important mediators of diabetes-accompanied brain dysfunction.