Ma Xiaoqiong, Liu Guangyi, Wang Shuang, Chen Zhong, Lai Maode, Liu Ziyang, Yang Jun
Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, and Kidney Disease Center of the First Affiliated Hospital, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Nov 15;859(2):170-7. doi: 10.1016/j.jchromb.2007.09.027. Epub 2007 Oct 10.
Abnormal lipid metabolism has been implicated in the pathogenesis of many neural system diseases, including epilepsy. Pentylenetetrazol (PTZ)-induced kindling in rodents is considered a model of human absence epilepsy and myoclonic, generalized tonic-clonic seizure. In an effort to further understand the mechanism for PTZ-induced seizure, we analyzed crude lipids and sphingolipids in the cortex, hippocampus, and brain stem of normal and PTZ-rats using delayed extraction matrix-assisted laser desorption ionization time-of-flight mass spectrometry (DE MALDI-TOF-MS). It was found that phosphatidylcholines dominated the crude lipids in different tissues and there were no obvious differences in crude lipid profiles of different tissues between normal and PTZ-rats. However, ceramide, sphingomyelins, and ceramide-monohexoside were differently distributed in normal and PTZ-rats. Using the reference mass spectra method established in our laboratory, it was shown that sphingomyelins and ceramide-monohexoside levels were elevated in the brain tissues of PTZ-rats. Ceramide levels were found to be higher in brain stem than in cortex and hippocampus of normal rats, and PTZ caused a general decrease in ceramide levels. These data suggest that changes in sphingolipid metabolism contribute to PTZ-induced seizure.
异常脂质代谢与包括癫痫在内的许多神经系统疾病的发病机制有关。戊四氮（PTZ）诱导的啮齿动物点燃被认为是人类失神癫痫以及肌阵挛性、全身性强直阵挛性发作的模型。为了进一步了解PTZ诱导癫痫发作的机制，我们使用延迟提取基质辅助激光解吸电离飞行时间质谱（DE MALDI-TOF-MS）分析了正常大鼠和PTZ诱导大鼠的皮质、海马和脑干中的粗脂质和鞘脂。结果发现，磷脂酰胆碱在不同组织的粗脂质中占主导地位，正常大鼠和PTZ诱导大鼠不同组织的粗脂质谱没有明显差异。然而，神经酰胺、鞘磷脂和神经酰胺单己糖苷在正常大鼠和PTZ诱导大鼠中的分布不同。使用我们实验室建立的参考质谱方法表明，PTZ诱导大鼠脑组织中鞘磷脂和神经酰胺单己糖苷水平升高。发现正常大鼠脑干中的神经酰胺水平高于皮质和海马，而PTZ导致神经酰胺水平普遍下降。这些数据表明鞘脂代谢变化促成了PTZ诱导的癫痫发作。
