摘要
基于血清代谢组学探讨六君子汤治疗4-硝基喹啉-N-氧化物(4-nitroquinoline-N-oxide,4NQO)诱导食管癌模型小鼠的作用机制。选取35~45日龄小鼠100只,随机分为空白组、模型组、六君子汤低浓度组、六君子汤中浓度组、六君子汤高浓度组。除空白组外,其余小鼠自由饮用100μg·mL^(-1)的4NQO溶液16周,构建食管癌小鼠模型。六君子汤低、中、高浓度组分别用药物质量分数为18.2、36.4、54.6 g·kg^(-1)的定制饲料喂养,称量各组小鼠体质量和脏器质量计算脏器指数;采用苏木素-伊红(hematoxylin-eosin,HE)染色观察各组小鼠食管组织病理改变;超高效液相色谱-串联质谱(ultra performance liquid chromatography-mass spectrometry,UPLC-MS/MS)进行小鼠血清样本的代谢物采集,筛选潜在生物标志物及分析相关代谢通路。结果显示,模型组小鼠脾脏、胃脏器指数明显降低,肺、食管、肾的脏器指数明显升高,与模型组相比,六君子汤各浓度脏器指数无明显变化;HE结果显示,六君子汤能改善小鼠食管癌细胞浸润性生长及癌变情况;血清代谢组学分析筛选出9种六君子汤干预食管癌小鼠的潜在生物标志物,分别为尿刊酸(urocanic acid,UCA)、1-油酰甘油磷酸丝氨酸(1-oleoylglycerophosphoserine)、11-脱氧前列腺素E1(11-deoxy prostaglandin E1)、多肽链Leu-Glu-Lys-Glu、(±)4-羟基-5E,7Z,10Z,13Z,16Z,19Z-二十二碳六烯酸[(±)4-HDHA]、脲基琥珀酸(ureidosuccinic acid)、泛酸[(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid]、犬尿酸(kynurenic acid)和双环前列腺素E2(bicyclo prostaglandin E2),涉及的通路包括组氨酸、嘧啶、丙氨酸、天门冬氨酸、谷氨酸、泛酸和色氨酸代谢及辅酶a生物合成等。六君子汤对4NQO诱导的食管癌模型小鼠发挥治疗作用,其作用机制可能与调节小鼠体内氨基酸代谢、炎症反应和免疫功能有关。
This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice.One hundred mice of 35-45 days were randomized into blank,model,and low-,medium-,and high-concentration(18.2,36.4,and 54.6 g·kg~(-1),respectively) Liujunzi Decoction groups.The mice in other groups except the blank group had free access to the water containing 100 μg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer.The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction.The body weight and organ weights were weighed for the calculation of organ indexes.The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining.Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples,screen out potential biomarkers,and predict related metabolic pathways.Compared with the blank group,the model group showed decreased spleen and stomach indexes and increased lung,esophagus,and kidney indexes.Compared with the model group,Liujunzi Decoction groups had no significant changes in the organ indexes.The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells.A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study,which were urocanic acid,1-oleoylglycerophosphoserine,11-deoxy prostaglandin E1,Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid,ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid,kynurenic acid,and bicyclo prostaglandin E2,which were mainly involved in histidine,pyrimidine,alanine,aspartate,glutamate,pantothenate and tryptophan metabolism and coenzyme A biosynthesis.In summary,Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid meta
作者
尚艺婉
陈星
武颖烁
周哲旭
刘洋
刘娅茹
胡啸博
陈玉龙
SHANG Yi-wan;CHEN Xing;WU Ying-shuo;ZHOU Zhe-xu;LIU Yang;LIU Ya-ru;HU Xiao-bo;CHEN Yu-long(Traditional Chinese Medicine(Zhongjing)School,Henan University of Chinese Medicine,Zhengzhou 450046,China;Nanyang Medical College,Nanyang 473000,China;Henan Key Laboratory of Traditional Chinese Medicine Prescription and Syndrome Signaling,Henan University of Chinese Medicine,Zhengzhou 450046,China)
出处
《中国中药杂志》
CAS
CSCD
北大核心
2024年第2期461-470,共10页
China Journal of Chinese Materia Medica
基金
国家自然科学基金面上项目(82074313)
河南省“双一流”创建学科中医学科学研究专项(HSRP-DFCTCM-2023-7-18)。
