基于代谢组学探讨柴芍六君汤对肝郁脾虚型慢性萎缩性胃炎大鼠的中枢调节作用  

Exploring Central Regulatory Effect of Chaishao Liujuntang on Chronic Atrophic Gastritis Rats with Liver Depression and Spleen Deficiency Syndrome Based on Metabolomics

作　　者：洪银洁 涂文玲 朱景茹 罗文谦 黄凯悦 甘慧娟[1] HONG Yinjie;TU Wenling;ZHU Jingru;LUO Wenqian;HUANG Kaiyue;GAN Huijuan(School of Traditional Chinese Medicine(TCM),Fujian University of TCM,Fuzhou 350122,China;School of Basic Medicine,Zhejiang Chinese Medical University,Hangzhou 310053,China;Zhangzhou Traditional Chinese Medical Hospital,Zhangzhou 363000,China)

机构地区：[1]福建中医药大学中医学院,福州350122 [2]浙江中医药大学基础医学院,杭州310053 [3]福建中医药大学附属漳州中医院,福建漳州363000

出　　处：《中国实验方剂学杂志》2024年第2期148-155,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81873237);福建省教育厅科研项目(JAT210137);福建省自然科学基金项目(2021J01929);福建中医药大学校管课题(X2021010);第五批全国中医临床优秀人才研修项目(国中医药人教函[2022]239号)。

摘　　要：目的:基于超高效液相色谱质谱联用法(UPLC-MS)及非靶向代谢组学技术探讨柴芍六君汤对肝郁脾虚型慢性萎缩性胃炎(CAG)大鼠的中枢调节作用,并寻找大脑皮质、下丘脑与胃组织代谢状态的关联性。方法:将28只Wistar大鼠随机分为空白组8只和造模组20只,采用化学诱导+饥饱失常+慢性束缚+夹尾刺激的方法建立肝郁脾虚型CAG大鼠模型,成模大鼠随机分为模型组和柴芍六君汤组,每组8只,柴芍六君汤组大鼠灌胃给予5.1 g·kg^(-1)的柴芍六君汤中药煎液,空白组和模型组大鼠予等体积灭菌饮用水灌胃,持续4周。观察对比各组大鼠宏观表征、行为学指标和胃黏膜组织病理学改变,采用UPLCMS非靶向代谢组学技术探讨柴芍六君汤对肝郁脾虚型CAG大鼠大脑皮质、下丘脑和胃组织代谢物表达的影响,并用Pearson相关系数法分析不同组织代谢物之间的关联。结果:与模型组比较,柴芍六君汤组大鼠毛发色泽、精神状态和大便性状等宏观表征有所改善,旷场实验的跨格和直立次数显著增加,强迫游泳静止时间显著减少(P<0.01),胃黏膜萎缩程度减轻。各组大鼠大脑皮质的代谢数据共鉴定出3个共同的潜在生物标志物,但未富集到通路;在下丘脑中鉴定出26个共同的潜在生物标志物,涉及到的关键代谢通路主要富集于嘌呤代谢、甘油磷脂代谢、D-谷氨酰胺和D-谷氨酸代谢;在胃中鉴定出17个共同的潜在生物标志物,涉及到的关键代谢通路主要富集于硫胺素代谢,缬氨酸、亮氨酸和异亮氨酸生物合成,牛磺酸和亚牛磺酸代谢。不同组织的代谢物相关性分析筛选到多个氨基酸及其衍生物介导大鼠大脑皮质、下丘脑与胃之间的代谢联系。结论:肝郁脾虚型CAG大鼠大脑皮质、下丘脑和胃的代谢紊乱各有特征,主要表现为甘油磷脂类、脂肪酸类和胆汁酸类代谢物含量变化,并且柴芍六君汤可能通过纠正氨基酸代�Objective:Based on ultra performance liquid chromatography-mass spectrometry(UPLCMS)and non-targeted metabolomics technology to discuss the central regulatory effect of Chaishao Liujuntang on chronic atrophic gastritis(CAG)rats with liver-depression and spleen-deficiency,and to look for the correlation between cerebral cortex,hypothalamus and metabolic status of gastric tissues.Method:A CAG rat model with liver-depression and spleen-deficiency was established by chemical induction,hunger and satiety disorders,chronic restraint and tail clamping stimulation,lasting for 16 weeks.Twenty-eight Wistar rats were randomly divided into a blank group of 8 rats and a model group of 20 rats.After the completion of modeling,4 rats in the model group were taken to observe the pathological changes of gastric mucosa.The remaining model rats were randomly divided into a model group of 8 rats and a Chaishao Liujuntang group of 8 rats.Chaishao Liujuntang group rats were given 5.1 g·kg^(-1) by gavage,and the remaining rats were given equal volume sterilized water by gavage for 4 weeks.Macroscopic characteristics,behavioral indicators and histopathological changes of the gastric mucosa of rats in each group were observed and compared.UPLC-MS non-targeted metabolomics was used to explore the metabolic regulation effect of Chaishao Liujuntang on the cerebral cortex,hypothalamus and stomach tissues of CAG rats with liver-depression and spleen-deficiency.Pearson correlation coefficient method was used to analyze the correlation between different tissue metabolites.Result:Compared with the model group,the macroscopic characteristics of rats in Chaishao Liujuntang group were improved,such as hair color,mental state and stool properties,and the number of times of crossing and standing in the open field experiment was significantly increased,and the static time of forced swimming was significantly reduced(P<0.01),and the gastric mucosa atrophy was reduced.The metabolic data from the cerebral cortex of rats in each group identified a total

关 键 词：慢性萎缩性胃炎 柴芍六君汤 代谢组学 中枢神经系统 肝郁脾虚证 超高效液相色谱质谱联用法(UPLC-MS) 氨基酸代谢 

分 类 号：R22[医药卫生—中医基础理论] R573.3[医药卫生—中医学] R28[理学—分析化学] O657[理学—化学]