镇肝熄风汤对自发性高血压大鼠血压及粪便菌群的影响  

Effect of Zhengan Xifengtang on Blood Pressure and Fecal Microflora of Spontaneously Hypertensive Rats

作　　者：刘双芳 金华[1,2] 凌必时[1,2] 祁尚文 司美龙 张秋菊 王宇[1,2] LIU Shuangfang;JIN Hua;LING Bishi;QI Shangwen;SI Meilong;ZHANG Qiuju;WANG Yu(Gansu University of Chinese Medicine,Gansu Lanzhou 730000,China;Key Laboratory of Dunhuang Medicine,Ministry of Education,Gansu Lanzhou 730000,China)

机构地区：[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

出　　处：《中国实验方剂学杂志》2024年第13期76-85,共10页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金项目(81860832,82160886);甘肃省自然科学基金项目(20JR10RA315);甘肃中医药大学中医学一级学科“岐黄英才”导师专项基金项目(ZYXKBD-202203);甘肃省优秀研究生“创新之星”项目(2021CXZX-761);甘肃省自然科学基金优秀博士项目(22JR5RA579);2023年度甘肃省省级重点人才项目(甘组通字[2023]20号)。

摘　　要：目的:观察镇肝熄风汤对自发性高血压大鼠(SHR)血压及粪便菌群的影响。方法:9周龄雄性SHR75只随机分为SHR组、贝那普利组(1.00 mg·kg^(-1)·d^(−1))、镇肝熄风汤高剂量组(34.5 g·kg^(-1)·d^(−1))、中剂量组(17.25 g·kg^(-1)·d^(−1))、低剂量组(8.625 g·kg^(-1)·d^(−1)),同源9周龄雄性Wistar-Kyoto(WKY)大鼠15只为正常组,正常组、SHR组予等体积蒸馏水灌胃,连续干预8周,给药期间定期检测大鼠血压。干预结束后,用无菌冻存管收集新鲜粪便,进行16S扩增子信息采集与分析;收集大鼠血浆、海马及回肠组织,进行超高液相色谱串联质谱法(UPLC-MS/MS)检测。结果:镇肝熄风汤降低了SHR的收缩压和舒张压。与SHR组比较,镇肝熄风汤降低了SHR粪便菌群多样性;门水平,镇肝熄风汤增加了SHR疣微菌门(Verrucomicrobia)、放线菌门(Actinobacteria)物种相对丰度,降低了互养菌门(Synergistetes)、软壁菌门(Tenericutes)、Candidatus Saccharibacteria物种相对丰度。种水平,与SHR组比较,镇肝熄风汤增加了Blautia wexlerae、Fusicatenibacter saccharivorans、嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila)物种相对丰度;降低了薰衣草梭菌(Clostridium lavalense)、产丁酸肠杆菌(Intestinimonas butyriciproducens)、Acetatifactor muris、拉瓦异普雷沃菌(Alloprevotella rava)、缬草杆菌(Oscillibacter valericigenes)物种相对丰度。经Spearman相关分析,大鼠收缩压与产乙醇杆菌属(Ethanoligenens)、气球菌属(Aerococcus)、丁酸弧菌属(Butyrivibrio)、欧陆森氏菌属(Olsenella)、双歧杆菌属(Bifidobacterium)、梭菌属XIVBb(Clostridium XIVBb)、异杆菌属(Allobaculum)、梭菌杆菌属(Fusicatenibacter)物种相对丰度呈负相关,与异普雷沃菌(Alloprevotella)物种相对丰度呈正相关。镇肝熄风汤升高了SHR血浆、海马5-羟色胺(5-HT)、回肠5-羟吲哚乙酸(5-HIAA)含量,降低了回肠5-HT、血浆5-HIAA含量,且海马与回肠5-HT含量呈负相关。结论:镇�Objective:To observe the effect of Zhengan Xifengtang on blood pressure and fecal microflora of spontaneously hypertensive rats(SHRs).Method:A total of 75 male SHRs aged nine weeks were randomly divided into SHR group,Benazepril group(1.00 mg·kg^(−1)·d^(−1)),high-dose Zhengan Xifengtang group(34.5 g·kg^(−1)·d^(−1)),medium-dose Zhengan Xifengtang group(17.25 g·kg^(−1)·d^(−1)),and low-dose Zhengan Xifengtang group(8.625 g·kg^(−1)·d^(−1)).A total of 15 male Wistar-Kyoto(WKY)rats aged nine weeks were selected as the normal group.The normal group and SHR group were administrated with an equal volume of distilled water for eight weeks.During the administration,the blood pressure of the rats was measured regularly.After the intervention,fresh feces were collected with a sterile frozen storage tube,and 16S amplicon information was collected and analyzed.Plasma,hippocampus,and ileum of rats were collected for ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)detection.Result:Zhengan Xifengtang decreased the systolic blood pressure and diastolic blood pressure of SHRs.Compared with the SHR group,Zhengan Xifengtang decreased the diversity of fecal microflora of SHRs.At the phylum level,Zhengan Xifengtang increased the relative abundance of SHR Verrucomicrobia and Actinobacteria and decreased the relative abundance of Synergistetes,Tenericutes,and Candidatus Saccharibacteria.Compared with the SHR group,Zhengan Xifengtang increased the relative abundance of Blautia wexlerae,Fusicatenibacter saccharivorans,and Akkermansia muciniphila and decreased the relative abundance of Clostridium lavalense,Intestinimonas butyriciproducens,Acetatifactor muris,Alloprevotella rava,and Oscillibacter valericigenes.Spearman correlation analysis showed that the systolic blood pressure of rats was negatively correlated with the relative abundance of Ethanoligenens,Aerococcus,Butyrivibrio,Olsenella,Bifidobacterium,Clostridium XIVb,Allobaculum,and Fusicatenibacter and positively correlated with

关 键 词：镇肝熄风汤 高血压 粪便菌群 5-羟色胺(5-HT) 

分 类 号：R284[医药卫生—中药学] R285[医药卫生—中医学] R289R287R22R2-031R33R24