机构地区:[1]福建中医药大学中医证研究基地,福州350122 [2]福建中医药大学中医学院,福州350122
出 处:《中华中医药杂志》2024年第7期3650-3657,共8页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:国家自然科学基金面上项目(No.81873237);福建省自然科学基金面上项目(No.2021J01929);第五批全国中医临床优秀人才研修项目(No.国中医药人教函[2022]239号)。
摘 要:目的:从代谢组学的角度研究慢性萎缩性胃炎(CAG)肝郁脾虚证大鼠的生物学基础。方法:将22只Wistar大鼠随机分为两组:空白组(8只)和模型组(14只),空白组予正常饮食,模型组予氨水+脱氧胆酸钠+饮食不节+夹尾法复制CAG肝郁脾虚证大鼠模型。观察大鼠的一般情况,通过旷场实验观察大鼠的行为学改变;通过HE染色观察胃组织的形态学改变;运用液相色谱-质谱联用(LC-MS)分析CAG肝郁脾虚证大鼠粪便、血清和胃组织的代谢组学特征,并用关联分析法构建不同组织间代谢物和代谢途径的表达关系。结果:以P<0.05且变量投影重要度(VIP)>1为卡值,模型组与空白组比较,于粪便中鉴定出162种差异代谢物,血清中鉴定出112种差异代谢物,胃组织中鉴定出98种差异代谢物。以P<0.05且impact>0筛选差异代谢途径,于粪便中富集到88条代谢途径,筛选出3条代谢途径依次为卵巢类固醇生成、类固醇激素生物合成、亚油酸代谢;于血清中富集到109条代谢途径,筛选出前5条代谢途径依次为癌症的中心碳代谢、蛋白质消化和吸收、氨酰tRNA生物合成、GABA能突触、味觉转导;于胃组织中富集到112条代谢途径,筛选出前5条代谢途径依次为鞘磷脂信号通路、蛋白质的消化和吸收、皮质醇的合成和分泌、鞘磷脂代谢、库欣综合征;联合分析共筛选出10个差异代谢物和1条显著性相关代谢途径:氧化磷酸化。结论:CAG肝郁脾虚证大鼠的粪便、血清和胃组织存在不同的代谢组学改变,其生物学基础与氧化磷酸化有关。Objective:To study the biological basis of chronic atrophic gastritis(CAG)rats with liver depression and spleen deficiency syndrome from the perspective of metabolomics.Methods:Twenty-two Wistar rats were randomly divided into two groups,8 rats in the blank group and 14 rats in the model group.The blank group was given a normal diet,while the model group was given ammonia water+sodium deoxycholate+improper diet+tail clamping method to replicate the CAG rats with liver depression and spleen deficiency syndrome.The general condition of rats and their behavioral changes through open field experiments were observed;the morphological changes of gastric tissue were observed by using hematoxylin eosin(HE)staining method;liquid chromatography-mass spectrometry(LC-MS)was used to analyze the metabolomic characteristics of feces,serum,and gastric tissues in CAG rats with liver stagnation and spleen deficiency syndrome.Correlation analysis was used to construct the expression relationships of metabolites and metabolic pathways among different tissues.Results:Compared with the blank group,162 differential metabolites were identified in feces,112 differential metabolites were identified in serum,and 98 differential metabolites were identified in gastric tissue,with P<0.05 and VIP>1 as the threshold value.Differential metabolic pathways were screened for P<0.05 and impact>0,and 88 metabolic pathways were enriched in feces,three metabolic pathways were identified in order:ovarian steroidogenesis,steroid hormone biosynthesis,linoleic acid metabolism.A total of 109 metabolic pathways were enriched in serum,the top 5 identified metabolic pathways were:central carbon metabolism in cancer,protein digestion and absorption,aminoacyl tRNA biosynthesis,GABA ergic synapses,and taste transduction.A total of 112 metabolic pathways were enrichied in gastric tissue,the top 5 identified metabolic pathways were:sphingolipid signaling pathway,protein digestion and absorption,cortisol synthesis and secretion,sphingolipid metabolism and cushing sy
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