复方利血平氨苯蝶啶片调节大鼠肠道菌群抗高血压实验研究  

The antihypertensive effect of compound reserpine and triamterene tablets on the regulation of intestinal flora in rat

作　　者：姜瑜 刘珊 袁天翊 张雯 李莉[1] 王守宝 方莲花 杜冠华 JIANG Yu;LIU Shan;YUAN Tian-yi;ZHANG Wen;LI Li;WANG Shou-bao;FANG Lian-hua;DU Guan-hua(Beijing Key Lab of Drug Target Identification and Drug Screening,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050,China;Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]中国医学科学院、北京协和医学院药物研究所,北京市药物靶点研究与新药筛选重点实验室,北京100050 [2]广东药科大学,广州510006

出　　处：《中国新药杂志》2022年第11期1057-1065,共9页Chinese Journal of New Drugs

基　　金：国家“重大新药创制”科技重大专项资助项目(2018ZX09711001);国家重点研发计划(2018YFC0311003);北京市自然科学基金面上资助项目(7192131);中国医学科学院医学与健康科技创新工程(2020-I2M-1-003)。

摘　　要：目的:通过观察连续4周给予复方利血平氨苯蝶啶片对自发性高血压大鼠(spontaneously hypertensive rat,SHR)的血压以及肠道菌群的影响,探讨其作用与肠道菌群调控之间的关系。方法:将40只SHR大鼠随机分为模型组(SHR)、培哚普利组(P)、复方利血平氨苯蝶啶片低剂量组(JL)和高剂量组(JH),另设10只Wistar大鼠为正常对照组(WKY)。各组均采取灌胃给药连续4周。每周测定并记录血压,末次给药后检测尿液钠离子、钾离子和血清醛固酮(aldosterone,Ald)含量;采集粪便提取大鼠肠道微生物总RNA,通过16SrRNA高通量测序对肠道菌群进行测序分析。结果:与SHR组相比,给药4周后JH组大鼠的收缩压和舒张压显著降低(P<0.05)。与SHR组相比,JL组和JH组大鼠血清醛固酮含量降低、尿液钠离子含量显著升高(P<0.05)。JL组、JH组及P组干预后菌群丰度与多样性增加。关联性分析显示,SHR大鼠血清醛固酮含量与乳酸细菌科(Lactobacillaceae)、厚壁菌科(unclassified p Firmicutes)等丰度显著相关,尿液中钠离子含量与氨基酸球菌科(Acidaminococcaceae)、萨特菌科(Sutterellaceae)等丰度显著相关。结论:复方利血平氨苯蝶啶片可改善SHR大鼠菌群丰度与多样性,促进毛螺旋科菌属、普雷沃科菌属、Muribaculaceae、Blautia等有益菌生长,抑制梭状芽孢杆菌属等有害菌增殖,对其发挥抗高血压作用具有重要意义。Objective:To observe the effect and possible mechanism of compound reserpine and triamterene tablets on the intestinal flora of spontaneously hypertensive rats(SHRs)for four weeks and explore the relationship between the therapeutic effects and regulation of intestinal flora.Methods:Forty SHR rats were randomly divided into model group(SHR),perindopril group(P),compound reserpine and triamterene tablets low-dose group(JL)and high-dose group(JH).Ten inbred Wistar rats(Wistar-Kyoto,WKY)were used as normal control group(WKY).All groups were given intragastric administration for 4 weeks.The blood pressure was measured and recorded every week.After the last administration,the samples were taken.The levels of urine sodium and potassium ions were detected.The serum was collected to detect the content of vasoactive substances aldosterone(Ald).The feces samples were collected,and total RNA of rat intestinal microbes was extracted.Subsequently,the rat gut flora was sequenced and analyzed by 16 S rRNA high-throughput sequencing.Results:4 weeks after administration,high-dose compound reserpine and triamterene tablets and perindopril significantly reduced the systolic and diastolic blood pressure in SHR rats compared with model group(P<0.05).Low-dose and high-dose compound reserpine and triamterene tablets decreased serum aldosterone levels and increased urine sodium ions,both significantly(P<0.05).Compared with the model group,low-dose and high-dose compound reserpine and triamterene tablets and perindopril increased the abundance and diversity of flora to varying degrees after intervention.The correlation analysis showed that the serum aldosterone content of SHR rats was significantly correlated with the abundance of Lactobacillaceae and unclassified p Firmicutes.The sodium ion content in urine was significantly correlated with Acidaminococcaceae and Sutterellaceae.Conclusion:Compound reserpine and triamterene tablets can improve the abundance and diversity of flora in SHR rat,and promote the growth of beneficial bacteria s

关 键 词：高通量测序 复方利血平氨苯蝶啶片 自发性高血压大鼠 肠道菌群 醛固酮 钠离子 

分 类 号：R965[医药卫生—药理学]