【摘要】：研究目的:采用代謝組學方法探索支氣管哮喘慢性持續(xù)期虛寒證和虛熱證患者的小分子代謝物差異,研究揭示哮喘臨床證候表型與小分子代謝物之間的相關性,尋找哮喘證型的潛在生物標志物,為中醫(yī)辨證論治提供有效的靶點。研究方法:選取北京地區(qū)漢族哮喘慢性持續(xù)期患者20例(虛寒證與虛熱證各10例),身體健康的志愿者10例,取得受試者知情同意后,收集空腹外周抗凝血2ml,抗凝靜置,離心取血清,-80℃冰箱保存,進行氣相色譜-質譜聯(lián)用(GC-MS)分析,采用多維分析(0)PLS-DA和單維分析(t檢驗)相結合的辦法,來篩選組間差異代謝物(VIP1,p0.05)。通過MBRole與KEGG進行差異代謝物通路富集分析。研究結果:慢性持續(xù)期哮喘患者與健康對照組相比,共發(fā)現(xiàn)40種差異代謝物;虛寒證組與虛熱證組相比,共發(fā)現(xiàn)18種差異代謝物;既是哮喘相關小分子代謝物,又可以區(qū)分虛寒證和虛熱證兩種不同證型的小分子代謝物有4種,分別為:二十四碳烷(tetracosane)、4-氨基丁酸(4-aminobutyricacid)、苯甲酸甲酸(Benzoylformicacid)、異肌醇(Allo-inositol)。二十四碳烷主要作為色譜分析標樣及固定液;苯甲酰甲酸作為原料,可合成多種藥劑,比如胃潰瘍用藥胃長寧、抗膽堿藥阿托品、抗炎藥布洛芬等;異肌醇作為化學試劑;4-氨基丁酸主要功能在中樞神經(jīng)系統(tǒng)、腦部及生殖系統(tǒng),多種外周組織中也存在,與哮喘的診治相關。經(jīng)MBRole與KEGG分析哮喘虛寒證組和虛熱證組差異代謝物,發(fā)現(xiàn)β-丙氨酸代謝通路受到擾動。結論:1、支氣管哮喘慢性持續(xù)期患者與健康對照組相比小分子代謝物有顯著差異。2、哮喘虛寒證與虛熱證患者小分子代謝物有顯著差異。3、4-氨基丁酸(4-aminobutyric acid)可能是潛在鑒別支氣管哮喘慢性持續(xù)期虛寒證和虛熱證型的生物標記物。4、哮喘虛寒證組和虛熱證組β-丙氨酸代謝通路受到擾動。
[Abstract]:Objective: to explore the differences of small molecule metabolites in asthmatic patients with chronic asthmatic deficiency cold syndrome and deficiency heat syndrome by means of metabonomics, and to reveal the correlation between the phenotype of asthma clinical syndrome and small molecule metabolites. To search for potential biomarkers of asthma syndrome type and to provide effective targets for TCM syndrome differentiation and treatment. Methods: twenty patients with chronic duration of asthma (10 cases of deficiency cold syndrome and 10 cases of deficiency heat syndrome) and 10 healthy volunteers were selected from the Han nationality in Beijing area. After obtaining the informed consent of the subjects, the fasting peripheral anticoagulant 2ml was collected. Centrifuged serum samples were collected from refrigerator at 80 鈩，

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