摘要
目的:通过青礞石干预戊四氮(PTZ)点燃癫痫大鼠的脑组织代谢组学研究,探讨青礞石治疗癫痫可能的作用机制。方法:运用PTZ点燃法建立大鼠癫痫动物模型,实验分为空白组、模型组、卡马西平组、青礞石组。通过超高效液相色谱-四极杆飞行时间质谱法(UPLC/Q-TOF-MS)技术检测脑组织样品,利用偏最小二乘法-判别分析(PLS-DA)和SPSS 18.0软件等方式对实验结果进行统计分析。结果:建立了大鼠脑组织代谢指纹图谱、代谢轮廓图,显示各组代谢轮廓发生了明显的变化,各组间均能很好地分开,并且青礞石组较卡马西平组有更靠近空白组的趋势。筛选出了7个差异代谢物,包括磷脂酰丝氨酸(PS)(18∶0/18∶0),L-谷氨酸,二十二碳六烯酰基乙醇酰胺,花生四烯酸,葡糖鞘氨醇,胆甾烷-3,7,12,24,25-五醇,溶血磷脂酰胆碱(LysoPC)(P-18∶0)。除二十二碳六烯酰基乙醇酰胺和LysoPC(P-18∶0)外,青礞石对其他5个差异代谢物均有显著性干预调节作用。影响PTZ点燃大鼠发生代谢紊乱的可能代谢通路有12条,较为重要的代谢通路有3条,即D-谷氨酰胺和D-谷氨酸代谢,丙氨酸、天冬氨酸和谷氨酸代谢以及花生四烯酸代谢,其中又以D-谷氨酰胺和D-谷氨酸代谢最为重要。结论:从脑组织代谢组学分析来看,青礞石对PTZ癫痫大鼠具有明确的干预作用,这可能与其干预以上差异代谢物含量及相关代谢通路有关,可减少兴奋性神经递质对脑组织神经元的毒性作用以及抑制脑组织炎症的发展以维持脑细胞的生物学功能而减缓癫痫发生。
Objective:To explore the possible mechanism of Chloriti Lapis in the treatment of epilepsy by the metabonomics of brain tissue in pentylenetetrazol(PTZ)-kindled epileptic rats treated with Chloriti Lapis.Method:The epileptic animal model in rats was established by PTZ kindling,and the rats were divided into the control group,model group,carbamazepine group and Chloriti Lapis group. The brain tissue samples were detected by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF-MS),and the experimental results were statistically analyzed by partial least squares-discriminant analysis(PLS-DA)and SPSS 18.0. Result: The metabolic fingerprints and metabolic profiles of the rat brain tissue were established,which showed that the metabolic profiles of each group had changed significantly and could be separated well among the groups. Moreover,the Chloriti Lapis group had a tendency to be closer to the control group than the carbamazepine group. Seven differential metabolites were screened, including phosphatidylserine(PS)(18∶0/18∶0),L-glutamic acid,docosahexaenoyl ethanolamide,arachidonic acid,glucosylsphingosine, cholestane-3,7,12,24,25-pentol and lysophosphatidylcholine(LysoPC)(P-18∶ 0).Except for docosahexaenoyl ethanolamide and LysoPC(P-18∶0),Chloriti Lapis had significant intervening and regulating effects on the other five differential metabolites. There were 12 possible metabolic pathways that affected the metabolic disorder of PTZ-kindled rats,and 3 important metabolic pathways(pathway impact>0.1),namely,D-glutamine and D-glutamate metabolism,alanine,aspartate and glutamate metabolism,and arachidonic acid metabolism,among which D-glutamine and D-glutamate metabolism was the most important metabolic pathways. Conclusion:From this point of view,Chloriti Lapis has a clear intervention effect on PTZkindled epileptic rats,which may be related to the intervention of the above differential metabolite contents and related metabolic pathways. It can reduce the toxic effect of excitatory neurotransmitters on neurons in brain tissue and inhibit the development of inflammation in brain tissue,so as to maintain the biological function of brain cells and slow down the occurrence of epilepsy.
作者
刘圣金
吴露婷
马瑜璐
房方
杨文国
单晨啸
卞勇
严辉
张志杰
奥·乌力吉
段金廒
LIU Sheng-jin;WU Lu-ting;MA Yu-lu;FANG Fang;YANG Wen-guo;SHAN Chen-xiao;BIAN Yong;YAN Hui;ZHANG Zhi-jie;AO Wu-li-ji;DUAN Jin-ao(Key Laboratory of Chinese Medicinal Resources Recycling Utilization,National Administration of Traditional Chinese Medicine,National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine,Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,School of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China;Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;Inner Mongolia University For Nationalities,Tongliao 028000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第10期76-84,共9页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81673566,81303178)
全国矿物药资源普查项目(2019)
江苏省研究生科研与实践创新计划项目(KYCX18-1608)
2017年中医药公共卫生服务补助专项(财社[2017]66号)。
关键词
矿物药
青礞石
癫痫
戊四氮(PTZ)
脑组织
代谢组学
作用机制
mineral Chinese medicines
Chloriti Lapis
epilepsy
pentylenetetrazol(PTZ)
brain tissue
metabonomics
mechanism of action
