基于血清非靶向代谢组学的过敏性紫癜儿童血热妄行证和风热伤络证作用机制

Mechanism of Henoch-Sch?nlein Purpura Patients with Blood Heat Syndrome and Wind-Heat Injuring Collaterals Syndrome Based on Serum Nontargeted Metabolomics Technology

目的研究过敏性紫癜不同证候血清差异代谢物,探讨其证候物质基础,为过敏性紫癜中医证候的精准阐释和诊治提供借鉴。方法对150例过敏性紫癜血热妄行证患者、150例过敏性紫癜风热伤络证患者和75名健康志愿者的血清进行超高效液相色谱-质谱联用(Ultra-high-performance liquid chromatography-quadruple time-of-flight mass spectrometry,UPLC-Q-TOF/MS)分析,经主成分分析筛选证候相关的生物标志物,利用KEGG数据库对筛选的差异代谢物进行注释和通路富集。结果健康对照组与过敏性紫癜两个证型组的生物标志物5个:牛磺胆酸、UDP-L-鼠李糖、5-胸苷酸、磷脂酰胆碱、溶血卵磷脂,主要参与甘油磷脂代谢、亚油酸代谢、牛磺酸和低牛磺酸代谢、α-亚麻酸代谢、花生四烯酸代谢、嘧啶代谢和初级胆汁酸生物合成等。用于区分血热妄行组和风热伤络组的生物标志物8个:苯丁氮酮、花生四烯酸、孕烯醇酮、皮质醇、牛磺胆酸、胆酸、(-)-牛蒡子素、甘胆酸,主要参与初级胆汁酸生物合成、牛磺酸和低牛磺酸代谢、甾体激素生物合成、不饱和脂肪酸的生物合成、花生四烯酸代谢等。结论特异性生物标志物在一定程度上从微观层面揭示过敏性紫癜血热妄行证和风热伤络证的代谢本质,有助于过敏性紫癜的中医临床诊断和治疗。

Objective To explore the material basis of different patterns of Henoch-Sch?nlein purpura(HSP)by analyzing the serum metabolic profiles,and realize the aim of precision medical treatment.Methods The serum from 150 HSP with blood heat syndrome,150 HSP with wind-heat injuring collaterals syndrome and 75 healthy volunteers were analyzed by ultra-high-performance liquid chromatography-quadruple time-of-flight mass spectrometry(UPLC-Q-TOF/MS),the principal component analysis was used to screen syndrome-related biomarkers,and the KEGG database was used to annotate and enrich the pathways of the selected differential metabolites.Results When compared with the metabolites of the normal control group,there were five specific differential metabolites such as taurocholic acid,UDP-L-rhamnose,5-thymidylic acid,PC(24:0/22:0)and LysoPC(16:0)and the specific metabolic pathways involved glycerophospholipid metabolism,pyrimidine metabolism,primary bile acid biosynthesis,arachidonic acid metabolism,alpha-linolenic acid metabolism,taurine and hypotaurine metabolism,linoleic acid metabolism.There were 8 biomarkers used to distinguish the HSP with blood heat syndrome group and wind-heat injuring collaterals syndrome group,including phenylbutazone,arachidonate,allopregnanolone,cortisol,taurocholic acid,boldione,(-)-Arctigenin and glycocholic acid,and the specific metabolic pathways involved arachidonic acid metabolism,steroid hormone biosynthesis,primary bile acid biosynthesis,taurine and hypotaurine metabolism and biosynthesis of unsaturated fatty acids.Conclusion These differential biomarkers reveal the mechanism of the syndromes of HSP from the microscopic level,and are helpful for the clinical diagnosis and treatment of HSP in traditional Chinese medicine.