过敏性鼻炎患者血清游离脂肪酸谱的研究
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摘要
目的探讨过敏性鼻炎患者血清游离脂肪酸(FFA)代谢谱的变化,为过敏性鼻炎的诊断寻找潜在的生物标志物。方法选择2016年10月～12月上海市宝山区中西医结合医院门诊过敏性鼻炎(AR)患者20例(病例组)及同期健康体检者20例(对照组)。采用气相-质谱联用(GC/MS)法检测两组血清游离脂肪酸水平;采用代谢组学分析方法分析两组血清中脂肪酸代谢谱的变化。结果两组血清游离脂肪酸谱分离趋势良好。两组筛选出了棕榈酸(C16:0)、十七酸(C17:0)、硬脂酸(C18:0)、亚油酸(C18:2)、花生酸(C20:0)、二十一酸(C21:0)、榆树酸(C22:0)7个有显著差异的脂肪酸(P<0.01)。对7个显著差异的脂肪酸进行ROC曲线绘制并计算ROC曲线下的面积:C16:0为0.778,C17:0为0.785,C18:0为0.830,C18:2为0.72,C20:0为0.83,C21:0为0.783,C22:0为0.840。结论过敏性鼻炎的发生与体内脂代谢紊乱有关,可将棕榈酸(C16:0)、十七酸(C17:0)、硬脂酸(C18:0)、亚油酸(C18:2)、花生酸(C20:0)、二十一酸(C21:0)、榆树酸(C22:0)作为过敏性鼻炎的潜在生物标志物。
Objective To investigate the changes of metabolic profiles of serum free fatty acid(FFA) in patients with allergic rhinitis and find potential biomarkers for the diagnosis of allergic rhinitis. Methods Serum free fatty acid levels in 20 normal subjects(control group) and 20 patients with allergic rhinitis(case group) were measured by gas chromatography-mass spectrometry(GC/MS) method. The principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) analysis were used to analyze changes in the profile of fatty acid metabolism in the patient's serum based on metabolomic analysis. Results The serum free fatty acid spectrum of allergic rhinitis group and normal control group had a good separation trend. By partial least squares-discriminant analysis, palmitic acid(C16:0), heptadecanoic acid(C17:0), stearic acid(C18:0), linoleic acid(C18:2), arachidic acid(C20:0), palmitic acid(C21: 0), cinereic acid(C22:0) were screened between allergic rhinitis group and normal control group, and the 7 fatty acids had significant differences between the groups(P<0.01). The ROC curve was plotted for seven significantly different fatty acids, and the area under the ROC curve was calculated. The area under the C16:0 curve was 0.778, and the area under the C17:0 was 0.785,. The area under the C18:0 curve is 0.830, the area under the C18:2 curve is 0.72, the area under the C20:0 curve is 0.83, the area under the C21:0 curve is 0.783, and the area under the C22:0 curve is 0.840. Conclusion The occurrence of allergic rhinitis is related to the disorder of lipid metabolism in the body, palmitic acid(C16:0), heptadecanoic acid(C17:0), stearic acid(C18:0), linoleic acid(C18:2), peanuts Acid(C20:0), palmitate(C21:0), citric acid(C22:0) are potential biomarkers for allergic rhinitis.
Objective To investigate the changes of metabolic profiles of serum free fatty acid(FFA) in patients with allergic rhinitis and find potential biomarkers for the diagnosis of allergic rhinitis. Methods Serum free fatty acid levels in 20 normal subjects(control group) and 20 patients with allergic rhinitis(case group) were measured by gas chromatography-mass spectrometry(GC/MS) method. The principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA) analysis were used to analyze changes in the profile of fatty acid metabolism in the patient's serum based on metabolomic analysis. Results The serum free fatty acid spectrum of allergic rhinitis group and normal control group had a good separation trend. By partial least squares-discriminant analysis, palmitic acid(C16:0), heptadecanoic acid(C17:0), stearic acid(C18:0), linoleic acid(C18:2), arachidic acid(C20:0), palmitic acid(C21: 0), cinereic acid(C22:0) were screened between allergic rhinitis group and normal control group, and the 7 fatty acids had significant differences between the groups(P<0.01). The ROC curve was plotted for seven significantly different fatty acids, and the area under the ROC curve was calculated. The area under the C16:0 curve was 0.778, and the area under the C17:0 was 0.785,. The area under the C18:0 curve is 0.830, the area under the C18:2 curve is 0.72, the area under the C20:0 curve is 0.83, the area under the C21:0 curve is 0.783, and the area under the C22:0 curve is 0.840. Conclusion The occurrence of allergic rhinitis is related to the disorder of lipid metabolism in the body, palmitic acid(C16:0), heptadecanoic acid(C17:0), stearic acid(C18:0), linoleic acid(C18:2), peanuts Acid(C20:0), palmitate(C21:0), citric acid(C22:0) are potential biomarkers for allergic rhinitis.
引文
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[11] 武玉凤,黎海芪.多不饱和脂肪酸预防过敏性疾病的研究进展[J].国际儿科学杂志,2011,38(4):374-376
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[14] 徐佩茹,李敏.过敏性鼻炎的诊断与治疗新进展[J].临床儿科杂志,2007,25(1):4-7.
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[16] 杜进涛,巴罗,尚婷婷,等.白细胞介素-17在A R及鼻息肉患者血液和组织中的表达 [J].四川大学学报:医学版,2010,41(2):235-238.
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[19] Boden G She P,Mozzoli M,et a1.Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver[J].Diabetes,2005,54(12):3458-3465.
[20] Weisberg SP,McCann D,Desai M,et al.Obesity is associated with Macrophage accumulation in adipose tissue[J].Journal of Clinical Investigation,2003,112(12):1796-1808.
[21] Chung S,Brown JM,Provo JN,et al.Conjugated linoleic acid promotes Human adipocyte insulin resistance through NFkappaB-dependent cytokine production[J].The Journal of Biological Chemistry,2005,280(46):38445-38456.
[22] Gao Z,Zhang X,Zuberi A,et al.Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes[J].Molecular Endocrinology,2004,18(8):2024-2034.
[23] Medzhitov R.Toll-like receptors and innate immunity[J].Nature Reviews Immunology,2001,l(2):135-145.
[24] Benitez S,Sanehez-Q uesada JL,Lueero L.et al.Changes in low-density lipoprotein electronegativity and oxidizability after aerobic exercise are related to the increase in associated non-esterified fatty acids.Atherosclerosis,2002,160:223-232.
[2] 王晓平.温阳通窍汤治疗过敏性鼻炎的临床观察[J].中医耳鼻喉科学研究杂志,2007,6(4):25.
[3] 张小玲.劫敏颗粒治疗过敏性鼻炎60例[J].陕西中医,2009,30(8):1020-1021.
[4] 张冬林.小青龙汤治疗过敏性鼻炎临床观察[J].亚太传统医药,2009,5(12):23-24.
[5] LehmanJM,BlaissMS.Pharmacotherapy of allergic rhinitiS[J].Allergy Frontiers,2010,5:19-28.
[6] 中华耳鼻咽喉头颈外科杂志编委会,中华医学会耳鼻咽喉头颈外科学分会鼻科学组.变应性鼻炎诊断和治疗指南[J].中国临床医生.2010,38(6):67-68.
[7] Boden G,She PMozzoli M,et al.Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver[J].Diabetes,2005,54(12):3458-3465.
[8] 王文静,冯琴,胡义扬.不饱和脂肪酸与非酒精性脂肪性肝病[J].中西医结合肝病杂志,2013,23(3):188-190.
[9] 钟纪茵,郭予雄,蒋卓勤.危重症患儿血清脂肪酸构成的临床研究[J].中国小儿急救医学,2008,15(4):332-335.
[10] 张志岐,束刚,方心灵,等.G蛋白偶联受体介导 FFA 的信号通路及生理功能[J].中国生物化学与分子生物学报,2009,25 (9):789-795 .
[11] 武玉凤,黎海芪.多不饱和脂肪酸预防过敏性疾病的研究进展[J].国际儿科学杂志,2011,38(4):374-376
[12] S?rensen JD,Olsen SF,Pedersen AK,et al.Effects of fish oil supplementation in the third trimester of pregnancy on prostacyclin and thromboxane production.American Journal of Obstetrics & Gynecology,1993,168(1);915-922.
[13] 朱秋蓓,张速勤,吴静娴,等.持续性变应性鼻炎患者鼻中隔中枢神经肽的初步研究[J].临床耳鼻咽喉头颈外科杂志,2009,23(3):339-343.
[14] 徐佩茹,李敏.过敏性鼻炎的诊断与治疗新进展[J].临床儿科杂志,2007,25(1):4-7.
[15] 俞海安,毕致,肖峰,等.鼻中隔偏曲合并变应性鼻炎患者手术治疗初步分析[J].中华耳鼻咽喉颈外科杂志,2008,43(7):537-538.
[16] 杜进涛,巴罗,尚婷婷,等.白细胞介素-17在A R及鼻息肉患者血液和组织中的表达 [J].四川大学学报:医学版,2010,41(2):235-238.
[17] 陈冬,李玉晓,李添应,等.实验性过敏性鼻炎大鼠血浆细胞因子IL-4和IFN-γ时相的变化[J].中华临床免疫和变态反应杂志,2009,4(3):254-258
[18] Itani SI,Ruderman NB,Schmieder F,et al.Lipid-induced insulin resistance in human muscle is associated with changes in diacylglycerol,protein kinase C,and IkappaB-alpha[J].Diabetes,2002,5 1(7):2005-2011.
[19] Boden G She P,Mozzoli M,et a1.Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver[J].Diabetes,2005,54(12):3458-3465.
[20] Weisberg SP,McCann D,Desai M,et al.Obesity is associated with Macrophage accumulation in adipose tissue[J].Journal of Clinical Investigation,2003,112(12):1796-1808.
[21] Chung S,Brown JM,Provo JN,et al.Conjugated linoleic acid promotes Human adipocyte insulin resistance through NFkappaB-dependent cytokine production[J].The Journal of Biological Chemistry,2005,280(46):38445-38456.
[22] Gao Z,Zhang X,Zuberi A,et al.Inhibition of insulin sensitivity by free fatty acids requires activation of multiple serine kinases in 3T3-L1 adipocytes[J].Molecular Endocrinology,2004,18(8):2024-2034.
[23] Medzhitov R.Toll-like receptors and innate immunity[J].Nature Reviews Immunology,2001,l(2):135-145.
[24] Benitez S,Sanehez-Q uesada JL,Lueero L.et al.Changes in low-density lipoprotein electronegativity and oxidizability after aerobic exercise are related to the increase in associated non-esterified fatty acids.Atherosclerosis,2002,160:223-232.