首页|小青龙汤颗粒治疗支气管哮喘慢性持续期寒证患者的代谢组学研究

小青龙汤颗粒治疗支气管哮喘慢性持续期寒证患者的代谢组学研究

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目的 评价小青龙汤颗粒治疗支气管哮喘慢性持续期寒证患者的临床疗效,探索其治疗机制.方法 随机双盲对照试验.选择2021年1月-2022年1月中国中医科学院广安门医院呼吸科60例患者作为观察对象,采用随机数字表法分为2组,每组30例.对照组给予西医常规疗法+安慰剂颗粒,试验组给予西医常规疗法+小青龙汤颗粒.2组均治疗2周,随访4周.分别于治疗前后进行中医证候及临床症状评分,采用哮喘控制测试问卷(ACT)评估哮喘控制情况,哮喘生命质量调查问卷(Mini-AQLQ)评估哮喘对患者生理及心理的影响;采用德国耶格肺功能仪检测FEV1、FEV1/FVC,采用呼出气一氧化氮(FeNO)检测仪器观察50ml/s流速时FeNO的变化,采用液质联用(LC-MS)进行非靶向代谢组学分析;观察治疗期间不良反应,评价药物安全性.结果 最终纳入47例,其中试验组24例、对照组23例.小青龙汤颗粒能够降低哮喘慢性持续期寒证患者中医证候积分(P<0.05),且试验组治疗2周、随访4周临床症状总分[3.00(1.00,4.00)分、3.00(0.00,4.00)分比3.5(3.00,5.00)分,Z=8.62]、喘息[1.00(0.00,1.00)分、1.00(0.00,1.00)分比 1.00(0.75,2.00)分,Z=6.80]及咳嗽[0.50(0.00,1.00)分、1.00(0.00,1.00)分 比 1.00(0.00,1.25)分,Z=6.12]评分较同组治疗前降低(P<0.01 或 P<0.05);试验组随访 4 周 ACT 评分[22.50(21.00,24.00)分比 19.00(15.00,21.50)分,Z=-4.87]、Mini-AQLQ 评分[(78.5±12.46)分比(71.27±9.70)分,t=-2.46]及对照组随访4周 ACT评分[24.00(19.00,25.00)分比21.5(8.00,23.00)分,Z=-3.18]较同组治疗前升高(P<0.01或P<0.05).试验组随访4周FEV1[2.96(2.27,3.49)L 比 2.60(2.32,3.49)L,Z=-3.72]、FEV 1/FVC[(80.83±6.84)%比(77.46±8.15)%,t=-2.32]及 FeNO[24.00(12.50,31.00)ppb 比 30.00(17.00,91.00)ppb,Z=-3.72]水平较同组治疗前升高(P<0.01或P<0.05).通过LC-MS技术分析,试验组同组治疗前后差异代谢物75种,2组治疗后差异代谢物295种.对差异代谢物进一步取交集,发现主要聚集于组氨酸代谢通路、磷酸盐和磷酸盐代谢通路;涉及相关代谢物为2-氨乙基磷酸盐、硫代丙二酸.结论 小青龙汤颗粒可有效改善哮喘慢性持续期寒证患者的中医证候、临床症状,尤其对喘息、咳嗽、胸闷有较好疗效,可升高患者FEV1、FEV1/FVC,降低FeNO水平.通过代谢组学研究,推测小青龙汤颗粒可能通过硫代丙二酸调控组氨酸代谢通路,发挥治疗哮喘的作用.
Study on metabolomics of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma
Objective To evaluate the clinical efficacy of Xiaoqinglong Decoction Granules in the treatment of chronic persistent cold syndrome of bronchial asthma;To explore its treatment mechanism.Methods A randomized double-blind controlled study was performed.Totally 60 patients from the Respiratory Department of Guang'anmen Hospital,Chinese Academy of Traditional Chinese Medicine from January 2021 to January 2022 were selected as the observation subjects.They were divided into two groups using a random number table method,with 30 cases in each group.The control group was given conventional treatment plus placebo,and the experimental group was given conventional treatment plus Xiaoqinglong Decoction Granules.The treatment for both group lasted for 14d.TCM syndromes and clinical symptoms before and after treatment were scored.Asthma Control Test Questionnaire(ACT)was used to evaluate asthma control status,and the Asthma Quality of Life Questionnaire(Mini AQLQ)was used to evaluate the physiological and psychological effects of asthma on patients;FEV1 was detected using a German Jaeger lung function instrument FEV1/FVC.A exhaled nitric oxide(FeNO)detection instrument was used to observe the changes in FeNO at a flow rate of 50 ml/s,and non-targeted metabolomics analysis was performed using liquid chromatography-mass spectrometry(LC-MS);adverse reactions were observed during treatment and drug safety was evaluated.Results Eventually 47 cases were included,24 cases of test group and of 23 cases of control group.Xiaoqinglong Decoction Granules could reduce the TCM syndrome score of patients with chronic duration cold syndrome of asthma(P<0.05).2 weeks after treatment,follow up for 4 weeks experimental group clinical symptom score[3.00(1.00,4.00),3.00(0.00,4.00)vs.3.5(3.00,5.00),Z=8.62],breathing symptom scores[1.00(0.00,1.00),1.00(0.00,1.00)vs.1.00(0.75,2.00),Z=6.80],cough symptom score[0.50(0.00,1.00),1.00(0.00,1.00)vs.1.00(0.00,1.25),Z=6.12]were lower than those in the experimental group before treatment in the same group(P<0.01 or P<0.05).The ACT score of the experimental group at 4 weeks of follow-up was[22.50(21.00,24.00)vs.9.00(15.00,21.50),Z=-4.87],Mini AQLQ score(78.5±12.46 vs.71.27±9.70,t=-2.46)and the control group had an ACT score of[24.00(19.00,25.00)vs.21.5(8.00,23.00)Z=-3.18]at 4 weeks of follow-up was higher than before treatment in the same group(P<0.01 or P<0.05).The experimental group was followed up for 4 weeks with a FEV1 of[2.96(2.27,3.49)L vs.2.60(2.32,3.49)L,Z=-3.72],FEV1/FVC[(80.83±6.84)%vs.(77.46±8.15)%,t=-2.32]and FeNO[24.00(12.50,31.00)ppb vs.30.00(17.00,91.00)ppb,Z=-3.72]was higher than before treatment in the same group(P<0.01 or P<0.05).Through LC-MS technique analysis,there were 75 kinds of different metabolites between the experimental group before and after treatment,and 295 kinds of different metabolites between the control group and the experimental group after treatment.Further intersection of differential metabolites showed that they were mainly concentrated in histidine metabolic pathway,phosphonate metabolic pathway and phosphate metabolic pathway.Related metabolites 2-aminoethyl phosphonate and thiomalonic acid were involved.Conclusions Xiaoqinglong Decoction Granules can effectively improve the TCM syndrome and clinical symptoms of patients with chronic persistent cold syndrome of asthma,especially for wheezing,cough and chest tightness,which can improve the levels of FEV1 and FEV1/FVC in patients and effectively reduce FeNO.Through metabolomics studies,it is speculated that Xiaoqinglong Decoction Granules may play a role in the treatment of asthma by regulating histidine metabolism pathway through thiomalonic acid.

AsthmaBronchiStatus asthmaticusXiao Qing Long TangMetabolomicsRandomized controlled study

王秋铭、李萌、张雯静、何轩辉、刘世刚、李辉

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中国中医科学院广安门医院呼吸科,北京 100053

中国中医科学院广安门医院免疫学研究室,北京 100053

哮喘 支气管 哮喘持续状态 小青龙汤 代谢组学 随机对照研究

2024

国际中医中药杂志
中华医学会,中国中医科学院中医药信息研究所

国际中医中药杂志

CSTPCD
影响因子:0.411
ISSN:1673-4246
年,卷(期):2024.46(12)