文献类型：期刊文献

中文题名：自发性高血压大鼠的中医证型特点及其代谢物质基础研究

英文题名：Study on the characteristics of Chinese medicine syndromes and its basic metabolites of spontaneously hypertensive rats

作者：张秋菊[1,2];王宇[1,2];凌必时[1];司美龙[1];孟浩先[1];田萌媛[1];张铭[1];连妮妮[1];康万荣[1,2];金华[1,2]

第一作者：张秋菊

机构：[1]甘肃中医药大学,兰州730000;[2]敦煌医学与转化教育部重点实验室,兰州730000

第一机构：甘肃中医药大学

年份：2025

卷号：33

期号：1

起止页码：44

中文期刊名：中国实验动物学报

外文期刊名：Acta Laboratorium Animalis Scientia Sinica

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82160886,81860832);甘肃省级重点人才基金资助项目(2023RCXM28);甘肃省自然基金项目(21JR7RA566);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金资助项目(ZYXKBD-202203);甘肃省中医药研究中心专项课题(zyzx-2020-zx7);甘肃省高校中(藏)药化学与质量研究省级重点实验室开放基金项目(zzy-2022-05)。

语种：中文

中文关键词：高血压;病证结合动物模型;自发性高血压大鼠;肝阳上亢证;非靶向代谢组

外文关键词：hypertension;disease and syndrome combined with animal model;spontaneously hypertensive rat;hyperactivity of liver yang;non-target metabolome

摘要：目的探究自发性高血压大鼠(spontaneously hypertensive rat,SHR)的中医证型特点及可能的代谢物质基础。方法10周龄SPF级SHR及同品系同周龄WKY大鼠,分SHR组和WKY组,每组8只大鼠。通过综合动态观察和检测SHR的一般状态、性情、周围血管充盈度、舌象、饮食饮水量、尿量、粪便量与性状、血压、心率、呼吸频率、痛阈和旷场实验,以辨别其可能的中医证型。同时,利用液相色谱串联质谱技术(liquid chromatography tandem-mass spectrometry,LC-MS/MS)对血清代谢物进行非靶向检测分析,以初步揭示引起血压升高和中医证型表现的物质基础。结果与WKY组相比,SHR组大鼠毛色暗黄、易激惹程度及周围毛细血管充盈评分较高(P<0.0001);舌色赤红,舌质干、津液少;24 h饮食饮水量及尿量、粪便量少(P<0.05),粪便含水率较低(P<0.001);收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、平均动脉压(mean arterial pressure,MAP)、心率(heart rate,HR)、呼吸频率(respiratory rate,RR)均明显较高(P<0.05);痛阈较低(P<0.0001);旷场实验显示,边缘运动距离和停留时间较长(P<0.001)。血清非靶向代谢组学结果显示,与WKY组相比,SHR组大鼠具有显著性差异的代谢物共有114种(P<0.05),这些差异代谢物主要为脂质和类脂分子(40.35%)、有机酸及其衍生物(22.8%)、有机杂环化合物(15.79%)。差异代谢物通过京都基因与基因组百科全书(kyoto encyclopedia of genes and genomes,KEGG)数据库富集分析共得到25条代谢通路,进一步差异丰度得分分析,其中16条通路被激活,仅4条通路被抑制,5条通路未见明显变化;而其中与神经系统兴奋性相关的3条通路中,谷氨酸能突触(glutamatergic synapse)和γ-氨基丁酸能突触(GABAergic synapse)被激活,而5-羟色胺能突触(serotonergic synapse)则被抑制。结论SHR有急躁易怒、周围血管扩张侧支循环形成、球结膜充血膨出、舌色赤红,舌质干、便秘、小便少而赤黄、心率、呼吸频率增快等表现,这些均提示SHR表现为高血压肝阳上亢证,其物质基础除了与脂类、氨基酸、碳水化合物代谢增强有关外,还可能与谷氨酸能、γ-氨基丁酸能及血清素能等神经通路代谢紊乱有关。
Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P<0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P<0.05),fecal water content was lower(P<0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P<0.05);Lower pain threshold(P<0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P<0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P<0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35%),organic acids and derivatives(22.8%),and organoheterocyclic compounds(15.79%).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.