蒙药蜀葵花醇提物利尿作用的血清代谢通路分析  

Analysis of serum metabolic pathways for diuretic effect of alcohol extract of Mongolian medicine Marshmallow flower

作　　者：陈玉花[1] 孟香花 包桂花[2] 肖田梅[1] 美丽 白梅荣[2] CHEN Yuhua;MENG Xianghua;BAO Guihua;XIAO Tianmei;MEI Li;BAI Meirong(College of Chemistry and Materials Science,Inner Mongolia University for Nationalities,Tongliao 028000,China;Key Laboratory of Ministry of Education of Mongolian Medicine R&D Engineering of Inner Mongolia University for Nationalities,Tongliao 028000,China)

机构地区：[1]内蒙古民族大学化学与材料学院,通辽028000 [2]内蒙古民族大学蒙医药研发工程教育部重点实验室,通辽028000

出　　处：《中华中医药杂志》2023年第10期4871-4876,共6页China Journal of Traditional Chinese Medicine and Pharmacy

基　　金：蒙药安全性评价创新团队项目(No.MY20190003);中央支持地方建设专项资金交叉学科建设项目(No.JCHXKXM001);自治区高校创新团队项目(No.NMGIRT2216);自治区高校科学技术研究项目(No.NJZY22473)。

摘　　要：目的:分析蒙药蜀葵花醇提物的利尿作用及机制。方法:将大鼠分为模型组,阳性对照组,蜀葵花醇提物高、中、低剂量组(以下简称高、中、低剂量组)。各给药组灌胃14 d药物溶液,在第14天时各组大鼠制备水负荷模型后给药,开始记录其各组大鼠不同时间点累积尿量。按照试剂盒说明检测Na^(+)、K^(+),Cl^(-)、cGMP、cAMP、AQP-1、AQP-2、ADH、ANP、ALD含量,采用LC-MS非靶向代谢组学技术分析血清内源性代谢产物变化。结果:与模型组比较,低剂量组给药第4—6小时后的累积尿量显著增加(P<0.05),高剂量组尿量从4 h开始到24 h内持续增加(P<0.05);高、中剂量组Na^(+)、Cl^(-)及K^(+)含量显著增加(P<0.05);低剂量组Na^(+)、Cl^(-)含量显著增加(P<0.05),高剂量组ANP含量显著增加(P<0.05),高和低剂量组ADH含量显著降低(P<0.05),中剂量组AQP-2含量显著降低(P<0.05);从血清中共筛选出28个差异内源性代谢物,其中上调5个、下调23个,主要涉及cAMP信号通路及多种氨基酸代谢。结论:蜀葵花具有明显的利尿作用,该结果与临床实践相符;蜀葵花促进尿液排泄的作用机制为先诱导ANP分泌进而抑制ADH分泌和释放、减少AQP-2在集合管主细胞管腔侧的穿梭,促进水钠的体外排泄量,维持机体电解质水平的平衡。该机制与蜀葵花调节cAMP信号通路和氨基酸代谢有关。Objective:To analyze the diuretic effect and mechanism of the alcohol extract of Mongolian medicine Marshmallow flower.Methods:The rats were divided into model group,positive control group,high,medium and low dose groups of the alcohol extract of Mongolian medicine Marshmallow flower.Each administration group was intragastric with drug solution for 14 days.On the 14th day,water load model was prepared for all group rats before administration,and the urine volume accumulated at different time points in each group was recorded.The contents of Na^(+),K^(+),Cl^(-),cGMP,cAMP,AQP-1,AQP-2,ADH,ANP and ALD were detected according to the kit instructions,serum endogenous metabolites were analyzed by LC-MS untargeted metabolomics.Results:Compared with the model group,the cumulative urine volume in the low dose groups increased significantly from 4 to 6th hour(P<0.05),and the urine volume in the high dose group increased continuously from 4 h to 24 h(P<0.05);The contents of Na^(+),Cl^(-) and K^(+)in the high and medium dose group were significantly increased(P<0.05);The contents of Na^(+) and Cl^(-) were significantly increased in the low dose group(P<0.05);ANP content in high dose group was significantly increased(P<0.05),ADH content in high and low dose groups was significantly decreased(P<0.05),AQP-2 content in medium dose group was significantly decreased(P<0.05);A total of 28 endogenous metabolites were screened from serum,including 5 up-regulated metabolites and 23 down-regulated metabolites,mainly involving cAMP signaling pathway and various amino acid metabolism.Conclusion:Marshmallow flower has obvious diuretic effect,which was consistent with clinical practice;The mechanism of promoting urine excretion of Marshmallow flower is to induce the secretion of ANP and then inhibit the secretion and release of ADH and reduce the shuttle of AQP-2 on the lumen side of the main cells in the collecting duct,promote the excretion of sodium and water in vitro,maintain the balance of electrolyte level.In summary,this mechanism is

关 键 词：蜀葵花醇提物 利尿 电解质 代谢组学 机制分析 蒙药 

分 类 号：R29[医药卫生—民族医学]