Compound 48/80诱导BN大鼠类过敏反应的蛋白组学研究
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摘要
目的探讨Compound 48/80诱导BN大鼠类过敏反应的发生机制,采用iTRAQ蛋白组学技术对类过敏的发生过程进行研究,并鉴定候选标志物。方法将BN大鼠按体质量随机分为对照1组、2组和Compound 48/80 1组、2组,每组各6只。对照组iv生理盐水5 mL/kg,Compound 48/80组分别iv Compound 48/80 2.5 mL/kg,取血浆样品经蛋白提取、电泳和质谱分析,确定类过敏反应差异蛋白。结果通过蛋白组学研究共鉴定10585个肽段,总共鉴定1987个蛋白质。提取7个与类过敏反应相关的差异蛋白。与对照组比较,Ica、Galectin-1上调;Hpse HEP、Mpo、MMP8、Hprt1、MMP9下调。结论Hpse HEP、Mpo、MMP8、Hprt1、Ica、MMP9、Galectin-1均可以作为类过敏反应的候选生物标志物。
Objective To investigate the mechanism of Compound 48/80-induced anaphylactoid reaction in BN rats, and ITRAQ proteomics technique was used to study the occurrence of anaphylaxis, and identify candidate markers. Methods BN rats were randomly divided into control group 1 and 2, Compound 48/80 group 1 and 2 according to body weight, and each group had 6 rats.Rats in control group were iv administered with normal saline 5 mL/kg, and Compound 48/80 groups were iv Compound 48/802.5 mL/kg. The plasma samples were analyzed by protein extraction, electrophoresis, and mass spectrometry to determine the differential proteins of anaphylactoid reaction. Methods A total of 10 585 peptide segments and 1 987 proteins were identified by proteomics. Seven differential proteins related to anaphylactoid reaction were extracted. Compared with the control group, Ica and Galectin-1 were up-regulated, and Hpse HEP, Mpo, MMP8, Hprt1, and MMP9 were down-regulated. Conclusion Hpse HEP, Mpo,MMP8, Hprt1, Ica, MMP9, and Galectin-1 can be used as candidate biomarkers for anaphylaxis.
Objective To investigate the mechanism of Compound 48/80-induced anaphylactoid reaction in BN rats, and ITRAQ proteomics technique was used to study the occurrence of anaphylaxis, and identify candidate markers. Methods BN rats were randomly divided into control group 1 and 2, Compound 48/80 group 1 and 2 according to body weight, and each group had 6 rats.Rats in control group were iv administered with normal saline 5 mL/kg, and Compound 48/80 groups were iv Compound 48/802.5 mL/kg. The plasma samples were analyzed by protein extraction, electrophoresis, and mass spectrometry to determine the differential proteins of anaphylactoid reaction. Methods A total of 10 585 peptide segments and 1 987 proteins were identified by proteomics. Seven differential proteins related to anaphylactoid reaction were extracted. Compared with the control group, Ica and Galectin-1 were up-regulated, and Hpse HEP, Mpo, MMP8, Hprt1, and MMP9 were down-regulated. Conclusion Hpse HEP, Mpo,MMP8, Hprt1, Ica, MMP9, and Galectin-1 can be used as candidate biomarkers for anaphylaxis.
引文
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[4]Xu Y,Dou D,Ran X,et al.Integrative analysis of proteomics and metabolomics of anaphylactoid reaction induced by Xuesaitong injection[J].J Chromatogr A,2015(1416):103-111.
[5]郭姗姗,王意忠,张毅,等.BN大鼠和豚鼠评价双黄连注射液的过敏反应[J].中国药理学与毒理学杂志,2009,23(2):128-133.
[6]Fairbanks M B,Mildner A M,Leoe J W,et al.Processing of the human heparanase procursor and evidence that the active enzyme is a heterodimer[J].J Biol Chem,1999,274(42):29587-29590.
[7]李素霞,袁勤生.类肝素酶[J].中国生化药物杂志,2002,23(2):104-107.
[8]Klebanoff S J,Kettle A J,Rosen H.,et al.Myeloperoxidase:a front-line defender against phagocytosed microoorganisms[J].J Leukoc Biol.,2013,93(2):185-198.
[9]Klebanoff S J.Myeloperoxidase:friend and foe[J].JLeukoc Bio,2005,77(5):598-625.
[10]Mathijsen R A,Huugen D,Hoebers N T,et al.Myeloperoxiedase is critically involved in the induction of organ damage after renal ischemia reperfusion[J].Am J Pathol,2007,171(6):1743-1752.
[11]Segura-Valdez L,Pardo A,Gaxiola M,et al.Upregulation of gelatinases a and B,collagenases 1 and 2,and increased parenchymal cell death in COPD[J].Cheat,2000,117(3):684-694.
[12]吴二喜,王凤飞,Mikie N.基质金属蛋白酶[J].生命科学研究,1999,3(3):175-194.
[13]Dumont O,Loufrani L,Henrion D.Key role of the NO-pathwayand matrix metalloprotease-9 in high blood flow induced remodeling of rat resistance arteries[J].Arterioscler Thromb Vasc Biol,2007,27(2):317-324.
[14]李骊华,雷寒.基质金属蛋白酶-9与动脉粥样硬化及斑块稳定性[J].中国老年学杂志,2009,29(6):771-773.
[15]Hüttner E,Speit G,Lambere B,et al.European HPRTworkshop in Collaboration with GUM GaterslebenQuedlinburg[J].Mutat Res,1996,359(1):71-76.
[16]丁慧,岳丽杰,杨春兰.次黄嘌呤鸟嘌呤磷酸核糖转移酶研究进展[J].遗传,2013,35(8):948-954.
[17]王丛珠,王登平.转铁蛋白介导作用的应用进展[J].放射免疫学杂志,2003,16(5):304-306.
[18]任声权.Galectin-1的生物活性及其研究进展[J].微生物学免疫学进展,2008,36(2):41-44.