乳源酪蛋白糖巨肽改善炎症性肠病的研究进展

摘要/Abstract

摘要： 乳源酪蛋白糖巨肽(CGMP)主要是κ-酪蛋白经凝乳酶降解产生的一类含有糖链的多肽，具有许多的生理活性功能和独特的营养特性，可广泛地应用于保健食品和医药品。本文首先概括CGMP的来源、结构特点及其研究开发现状，从炎症性肠病(IBD)的免疫病理机制的角度，对本实验室和国外在CGMP调理、改善和治疗IBD的相关研究进行系统地介绍，提出CGMP在一定程度上为IBD的生物免疫治疗提供了新的途径以及展示其广阔的开发前景。

关键词: 酪蛋白糖巨肽（CGMP）, 炎症性肠病（IBD）, 免疫调节, 肠道菌群

Abstract: Casein glycomacropeptide (CGMP) is mainly a class of peptides bearing carbohydrate chains derived from the hydrolysis of κ-casein by tenet. Because CGMP has many physiological functions and unique nutritional properties, it can be widely used in the fields of functional food and medicine. CGMP has been reported to have anti-inflammatory activity such as improvement and immunotherapy on inflammatory bowel disease (IBD). In this paper, the sources, structural characteristics and current research status of CGMP are outlined. Recent research advances in the regulatory, improving and therapeutic effects of CGMP on IBD are reviewed. Moreover, the future development prospects of CGMP are also proposed.

Key words: casein glycomacropeptide (CGMP), inflammatory bowel disease (IBD), immunoregulation, intestinal flora

中图分类号:

TS201.2

朱晨晨，陈庆森*. 乳源酪蛋白糖巨肽改善炎症性肠病的研究进展[J]. 食品科学, 2012, 33(1): 262-266.

参考文献

参考文献：
[1] SARTOR RB.Mechanisms of diseage:Pathogenesis of Crohn disease and ulcerative colitis[J].Nature Clinical Practice Gastroenterology&Hepatology.2006,3(7):390-407.
[2] XAVIER RJ,PODOLSKY DK.Unravealing the pathogenesis of inflammatory bowel diseaseJ].Nature,2007,448(7152):427-434.
[3] OH S,WOROBO RW,KIM B,et al.Detection of cholera toxin-binding activity of κ-casein macropeptide and optimization of its production by the response surface methodology[J].Bioscience,Biotechnology,and Biochemistry,2000,64(3):516-522.
[4] 曹晋宜,陈庆森.酪蛋白糖巨肽(CGMP)对小鼠盲肠中微生物区系的影响[J]. 食品科学, 2008,29(10):582-585.
[5] 曹晋宜,陈庆森,王友湘.酪蛋白糖巨肽(CGMP)对小鼠肠道菌群消长规律的影响[J].食品科学,.2007,28(11):536-540.
[6] OTANI H,HATA I.Inhibition of proliferative responses of mouse spleen lymphocytes and rabbit Peyer’s patch ceils by bovine milk caseins and their digests[J].Journal of Dairy Research,1995,62(2):339-348.
[7] 李伟,陈庆森.酪蛋白糖巨肽对小鼠肠道免疫系统的影响[J].食品科学,2010,31(15);240-243.
[8] ALAIS C,MOCQUOT G,NITSCHMANN H.Das Lab und seine Wirkung auf das Casein der Milch. VII. über die Abspalt ung von
Nicht-Protein-Stickstoff (NPN) aus Casein durch Lab und ihre Beziehung zur Prim?rreaktion der Labgerinnung der Milch[J].Helvetica
Chimica Acta,1953,36(7):1955-1968.
[9] DAVID F,WAUGH,PETER H.k-Casein and the stabilization of casein micelles[J].American Chemical Society,1956,78(18):4576-4582.
[10] DELFOUR A,JOLLèS J,ALAIS C.Caseino-glycopeptides: characterization of a methionine residue and of the N-terminal sequence[J]. Biochemical and Biophysical Research Communications,1965,19(4):452-455.
[11] BRODY E P.Biological activities of bovine glycomacropeptide[J].British Journal of Nutrition,2000, 84:39-46.
[12] FARRELL H M,JIMENEZ-FLORES R BLECK G T.Nomenclature of the proteins of cows' milk-sixth revision[J].Dairy Science,2004,87(6):1641-1674.
[13] FIAT A-M,JOLLèS P.Caseins of various origins and biologically active casein peptides and oligosaccharides:structural and physiological aspects. Molecular and Cellular Biochemistry[J],1989,87(1):5-30.
[14] PISANO A,PACKER N H,REDMOND J W.Characterization of O-linked glycosylation motifs in the glycopeptide domain of bovine k-casein[J].Glycobiology,1994,4(6):837-844.
[15] ZEVACO C,RIBADEAU-DUMAS B.A study on the carbohydrate binding sites of k-casein using high performance liquid chromatography[J].Milchwissenschaft,1984,39:206-210.
[16] SAITO T,YAMAJI A,ITOH T.A new isolation method of caseinoglycopeptide from sweet cheese whey[J].Dairy Science,1991,74(9):2831-2837.
[17] MORR C V,SEO A.Fractionation and characterization of glycomacropeptide from caseinate and skim milk hydrolysates[J]. Food Science,1988,53(1):80-87.
[18] LI E W Y,MINE Y.Technical note:comparison of chromatographic profile of glycomacropeptide from cheese whey isolated using different methods[J].Dairy Science,2004,87(1):174-177.
[19] TOLKACH A,KULOZIK U.Fractionation of whey proteins and caseinomacropeptide by means of enzymatic crosslinking and membrane separation techniques[J]. Food Engineering,2005,67(1):13-20.
[20] 李博智,闫亚丽,陈庆森.利用TGase结合微滤技术从乳清粉中分离纯化CGMP的研究[J].食品科学，2009,30(20):94-100.
[21] 陈绪卓,陈庆森.甜乳清粉中酪蛋白糖聚肽(CGMP)的分离及刺激小鼠肠道分泌IgA特性的研究[J].食品科学,2007,28(6):327-331.
[22] BONEN D K,CHO JH.The genetics of inflammatory boweldisease[J].Gastroenterology,2003,124(2):521-536.
[23] FUSS IJ,NEURATH M,BOIRIVANT M,et al.Disparate CD4+ lamina propria(LP)lymphokine secretion profiles in inflammatory bowel disease.Crohn’s disease LP cells manifest increased secretion of IFN-gamma，whereas ulcerative colitis LP cells manifest increased secretion of IL-5[J].Immunology,1996,157(3):1261-1270.
[24] HELLER F,FLORIAN P,BOJARSKI C,et al.Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelial tight junctions,apoptosis,and cell restitution[J].Gastroenterology,2005,129(2):550-564.
[25] HORI S,NOMURA T,SAKAGUCHI S.Control of regulatory T cell development by the transcription factor Foxp3[J].Science,2003,
299(5609):1057-1061.
[26] IZCUE A,COOMBES JL,Powrie F.Regulatory T cells suppress systemic and mucosal immune activation to control intestinal inflammation[J].Immunological Reviews,2006,212(1):256-271.
[27] MC GOVERN DP,ROTTER JI,MEI L,et al.Genetic epistasis of IL23/IL17 pathway genes in Crohn’s disease[J].Inflammatory Bowel Diseases,2009,15(6):883-889.
[28] SEIDERER J,ELBEN I,Diegelmann J,et al.Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease(IBD):upregulated colonic IL-17F expression in active Crohn’s disease and analysis of the IL17F p.His161Arg polymorphism in IBD[J].Inflammatory Bowel Diseases,2008,14(4):437-445.
[29] LAMKANFI M,KANNEGANTI TD,FRANCHI L,et al.Caspase-1 inflammasomes in infection and inflammation[J].Leukocyte Biology,2007,82(2):220-225.
[30] MAZMANIAN SK,ROUND JL,KASPER DL.A microbial symbiosis factor prevents intestinal inflammatory disease.Nature 2008;453:620-625
[31] SELLON RK,TONKONOGY S,SCHULTZ M,et al.Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice.Infection and Immunity,1998,66(11):5224-5231.
[32] 欧阳钦.炎症性肠病的病因和发病机制[J].实用医学杂志,2003,19(5):448-449.
[33] LOFTUS EV JR.Clinical epidemiology of inflammatory bowel disease:Incidence,prevalence,and environmental influences.
Gastroenterology,2004,126(6):1504-1517.
[34] 贾玉臣,陈庆森.乳源酪蛋白糖巨肽改善小鼠溃疡性结肠炎的研究[J].食品科学,2010,31(21):365-368.
[35] DADDAOUA A,PUERTA V,ZARZUELO A,et al.Bovine glycomacropeptide is anti-inflammatory in rats with hapten-induced colitis[J],Nutritional Immunology,2005,135(5):1164-1170.
[36] REQUENA P,DADDAOUA A,PLATA E M,et al. Bovine glycomacropeptide ameliorates experimental rat ileitis by mechanisms involving downregulation of interleukin 17[J].Pharmacology,2008,154,825-832.
[37] 贾玉臣,陈庆森.乳源糖巨肽对小鼠IFN-γ和IL-4的调节作用[J].中国乳品工业,2010,38(11):11-14.
[38] REQUENA P,GONZALEZ R,POSADAS R L,et al.The intestinal anti-inflammatory agent glycomacropeptide has immunomodulatory actions on rat splenocytes[J].Biochemical Pharmacology,2010(79):1797-1804.
[39] REQUENA P,DADDAOUA A,GUADIX E,et al.Bovine glycomacropeptide induces cytokine production in human monocytes through the stimulation of the MAPK and the NF-κB signal transduction pathways[J].British Journal of Pharmacology,2009,157(7):1232-1240.
[40] 曹晋宜,陈庆森.基于ERIC-PCR技术研究酪蛋白糖巨肽对小鼠肠道菌群结构的影响[J].中国微生态学杂志,2010,22(9):769-772.