基于核磁代谢组学的酒炙韭菜子温肾助阳作用机制研究  

Mechanism of Wine-processed ALLII TUBEROSI SEMEN on Wenshen(温肾)and Zhuyang(助阳)Based on 1H-NMR Metabonomics

作　　者：魏玉玲 赵慧亮 田俊生[2] 吴文辉 Wei Yuling;Zhao Huiliang;Tian Junsheng;Wu Wenhui(Department of Pharmacy,Chongqing Traditional Chinese Medicine Hospital,Chongqing 400021;Modern Research Center for Traditional Chinese Medicine,Shanxi University,Taiyuan 030006)

机构地区：[1]重庆市中医院药剂科,重庆400021 [2]山西大学中医药现代研究中心,太原030006

出　　处：《中药药理与临床》2022年第3期116-121,共6页Pharmacology and Clinics of Chinese Materia Medica

基　　金：重庆市自然科学基金(编号:CSTC2018JCYJAX0017);重庆市科研院所绩效激励引导专项(编号:CSTC2018JXJL10003);重庆市卫健委“十三五”市级中医药重点学科(渝中医[2018]43号)

摘　　要：目的:本研究旨在运用代谢组学技术探讨酒炙韭菜子对肾阳虚证模型大鼠的温肾助阳的增效作用机制。方法:将大鼠随机分为模型对照组、生品韭菜子11.1 g/kg组和酒炙韭菜子11.1 g/kg组,大鼠灌胃给予0.5%CMC-Na混悬液或相应药物,连续25 d,给药3 d后,肌肉注射氢化可的松琥珀酸钠25 mg/kg建立肾阳虚证大鼠模型,另设正常对照组。利用与能量代谢相关的药效学指标评价酒炙韭菜子温肾助阳的功效。采用^(1)H-NMR代谢组学技术对血清样本进行分析,寻找与酒炙韭菜子温肾助阳功效相关的差异代谢物,并对其关键代谢通路进行深度解析,阐释其作用机制。结果:与正常对照组大鼠相比,模型对照组大鼠血清中cAMP/cGMP比值明显下降、三酰甘油(TG)含量显著升高,而总胆固醇(TC)、葡萄糖(GLU)含量均显著下降,肝脏组织Na+-K+-ATP酶、Ca^(2+)-Mg^(2+)-ATP酶、琥珀酸脱氢酶(SDH)和乳酸脱氢酶(LDH)活力均显著降低(P<0.01);生品韭菜子对能量代谢指标调节作用较弱,而酒炙韭菜子除cAMP、TG含量明显降低外,上述其余指标均明显升高(P<0.05或P<0.01)。代谢组学结果表明给予酒炙韭菜子11.1 g/kg后,大鼠血清中6种差异代谢物水平与模型对照组比较均具有明显升高或降低,通路分析结果显示其调节作用涉及甘氨酸、丝氨酸和苏氨酸代谢、乙醛酸和二羧酸代谢、牛磺酸和亚牛磺酸代谢等多条作用途径的代谢通路。结论:酒炙韭菜子温肾助阳功效要优于生品韭菜子,其作用机制与调节体内多条代谢通路关系密切。Objective:To explore the synergistic mechanism of wine-processed ALLII TUBEROSI SEMEN(ATS)on Wenshen(温肾)and Zhuyang(助阳)of the rat with Shenyangxu(肾阳虚)syndrome by metabonomics technology.Methods:Rats were randomly divided into a model group,a crude ATS(11.1 g/kg)group,and a wine-processed ATS(11.1 g/kg)group.The corresponding drugs or 0.5%CMC-Na suspension were given to the corresponding groups for 25 d.After administration for 3 d,25 mg/kg hydrocortisone sodium succinate was injected to induce the rat model of Shenyangxu syndrome,and a normal control group was established.The pharmacodynamics indicators related to energy metabolism were used to evaluate the efficacy of wine-processed ATS.^(1)H-NMR metabonomics technology was used to analyze serum samples to find the differential metabolites related to the effect of wine-processed ATS on Wenshen and Zhuyang,and deeply analyzed key metabolic pathways to explain the mechanism.Results:As compared with the normal control group,the ratio of serum cAMP/cGMP was significantly decreased in the model group.The triglyceride(TG)content was significantly increased,and the total cholesterol(TC)and glucose(GLU)content were significantly decreased in the model group.The activities of Na+K+ATPase,Ca^(2+)Mg^(2+)ATPase,succinate dehydrogenase(SDH),and lactate dehydrogenase(LDH)in the liver tissue were significantly reduced(P<0.01).The crude ATS showed a weaker callback effect on the indicators of energy metabolism,while the wine processed ATS had an obvious callback effect(P<0.05 or P<0.01).The metabolomics results showed that as compared with the model group,the 6 differential metabolites in the serum of rats had a significant callback trend in the 11.1 g/kg wine processed ATS group.The results of pathway analysis showed that the regulatory effects involved various metabolic pathways including glycine,serine and threonine metabolic pathway,glyoxylate and dicarboxylate metabolic pathway,taurine and hypotaurine metabolic pathway.Conclusion:The wine processed ATS shows

关 键 词：酒炙韭菜子 温肾助阳 肾阳虚证 能量代谢相关酶 核磁代谢组学 代谢通路 

分 类 号：R285.5[医药卫生—中药学]