基于血清代谢组学分析哮喘宁治疗心理应激哮喘的作用机制  

Effects of Xiaochuanning(哮喘宁)on the Mechanism of Action in Treating Psychological Stress-Related Asthma Based on Serum Metabolomics Analysis

作　　者：程思益 黄贵锐 张诗瑜 崔红生 CHENG Siyi;HUANG Guirui;ZHANG Shiyu;CUI Hongsheng(Beijing University of Chinese Medicine Third Affiliated Hospital,Beijing 100029,China;Beijing University of Chinese Medicine,Beijing 100029,China)

机构地区：[1]北京中医药大学第三附属医院,北京100029 [2]北京中医药大学,北京100029

出　　处：《中医药导报》2025年第2期1-6,29,共7页Guiding Journal of Traditional Chinese Medicine and Pharmacy

基　　金：国家自然科学基金面上项目(82274497)。

摘　　要：目的:基于非靶向代谢组学技术探讨心理应激哮喘(PSA)小鼠的血清代谢物变化及哮喘宁治疗PSA的作用机制。方法:运用随机数字表法将32只SPF级雄性BALB/c小鼠分为正常组、哮喘组、心理应激哮喘组和中药组。除正常组外的小鼠第1、8天腹腔注射卵蛋白(OVA)和氢氧化铝混合液,第15天开始采用1%OVA溶液雾化激发建立哮喘模型,其中心理应激哮喘组、中药组从第1天起给予束缚刺激,连续束缚28 d,建立PSA模型。中药组小鼠从第15天起予哮喘宁连续给药14 d。第28天进行无创肺功能检测及旷场实验,实验结束后收集小鼠肺组织及血清,运用HE染色法观察肺组织病变,采用超高效液相色谱-质谱法(UPLC-MS)对各组小鼠血清样本小分子代谢产物进行分析,运用主成分分析法(PCA)及偏最小二乘判别法(PLS-DA)等统计学手段筛选特征代谢物质,并对筛选后的代谢物所涉及的生物代谢通路进行富集分析研究。结果:心理应激哮喘组与哮喘组相比,肺部炎症细胞浸润明显,肺通气功能特殊气道阻力(sRAW)升高,50%呼出量时的呼气流速(EF50)下降,旷场实验总运动距离和运动速度下降,内源性物质分离明显,筛选出差异代谢物89个,主要富集在精氨酸生物合成、β-丙氨酸代谢、不饱和脂肪酸生物合成、精氨酸和脯氨酸代谢、GABA能突触代谢通路。与心理应激哮喘组比较,哮喘宁对该组小鼠气道炎症、肺功能sRAW、EF50和旷场实验运动距离、运动速度具有回调作用,筛选出差异代谢物50个,主要富集在色氨酸代谢、味觉传导、突触小泡循环、苯丙氨酸、酪氨酸和色氨酸的生物合成代谢通路。结论:PSA小鼠内源性代谢物及代谢通路发生改变。哮喘宁可改善部分差异代谢物及代谢通路紊乱,进而改善哮喘的症状及抑郁状态。Objective:To explore the changes in serum metabolites in mice with psychological stress-related asthma(PSA)and the mechanism of action of Xiaochuanning in treating PSA based on untargeted metabolomics technology.Methods:Totally 32 SPF-level male BALB/c mice were distributed into four distinct clusters at random,including control group,asthma group,PSA group,and Chinese medicine group.Except for the control group,all other groups of mice received an intraperitoneal administration of a concoction containing ovalbumin and aluminum hydroxide on the 1st and 8th days.Subsequently,from the 15th day,they were exposed to an aerosol of 1%ovalbumin solution to induce the asthma model.The PSA and Chinese medicine groups received restraint stress from the 1st day for 28 consecutive days to establish the PSA model.The Chinese medicine group was administered Xiaochuanning continuously from 15th day for 14 days.Non-invasive lung function tests and open field tests were performed on 28th day.Samples of lung tissue and blood serum were gathered.Lung tissue was used for disease investigation with HE,and blood serum was analyzed to identify small-molecule metabolites using ultra-performance liquid chromatography linked with mass spectrometry(UPLC-MS).Principal component analysis(PCA)and partial least squares-discriminant analysis(PLS-DA)were used to screen differential metabolites and analyze metabolic pathways.Results:Compared with the asthma group,the PSA group exhibited significant pulmonary inflammatory cell infiltration,increased specific airway resistance(sRAW),decreased expiratory flow at 50%tidal volume(EF50),reduced total movement distance,and movement speed in the open field test,and significant separation of endogenous metabolites.A total of 89 differential metabolites were identified,mainly enriched in arginine biosynthesis,β-alanine metabolism,unsaturated fatty acid biosynthesis,arginine and proline metabolism,and GABA ergic synapse metabolic pathways.Compared with the PSA group,the Chinese medicine group showed improv

关 键 词：心理应激哮喘 哮喘宁 代谢组学 超高效液相色谱-质谱法(UPLC-MS) 小鼠 

分 类 号：R285.5[医药卫生—中药学]