乳铁蛋白的神经保护作用
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摘要
乳铁蛋白(Lf)是一种铁结合性糖蛋白,分子量为80 kDa,是转铁蛋白家族的成员。Lf属于一种多功能蛋白,具有促进肠道内铁吸收、抗癌、抗病毒、抗炎及免疫调节等作用。越来越多的研究表明,乳铁蛋白在神经保护方面具有一定作用。本文从乳铁蛋白减少淀粉样蛋白β沉积、抗氧化、降低神经炎症反应、促进钙稳态及调节信号通路等方面综述了乳铁蛋白对各种因素引起神经损伤的保护效应。
Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80 kDa and is a member of the transferrin family. Lactoferrin is a multifunctional protein, apart from promoting the absorption of iron in the intestine, which also has anti-cancer, antiviral, anti-inflammation, immune regulation functions and properties. More and more studies have shown that lactoferrin plays a role in neuroprotection. In this review, we summarized the protective effects of lactoferrin on nerve injury caused by various factors in terms of reducinge β-amyloid deposition, having antioxidant capacity, alleviatinge neuroinflammatory, preserving calcium homeostasis, and regulate regulating various signal transduction pathways.
Lactoferrin is an iron-binding glycoprotein with a molecular weight of about 80 kDa and is a member of the transferrin family. Lactoferrin is a multifunctional protein, apart from promoting the absorption of iron in the intestine, which also has anti-cancer, antiviral, anti-inflammation, immune regulation functions and properties. More and more studies have shown that lactoferrin plays a role in neuroprotection. In this review, we summarized the protective effects of lactoferrin on nerve injury caused by various factors in terms of reducinge β-amyloid deposition, having antioxidant capacity, alleviatinge neuroinflammatory, preserving calcium homeostasis, and regulate regulating various signal transduction pathways.
引文
[1]扈晓敏.乳铁蛋白免疫复合物活化人单核细胞的分子机制研究[D].苏州:苏州大学, 2016.
[2] Vorland LH. Lactoferrin:a multifunctional glycoprotein[J]. APMIS,1999, 107(11):971-981.
[3] Lian-da Q, Fan-ze P, Xi-lin H, et al. Minireview of Lactoferrin research in domestic and overseas[J]. Heilongjiang August First Land Reclamation University, 2005, 17(6):50-54.
[4]庞晓楠,弘笑,魏璇,等.乳铁蛋白的理化性质及其重组表达系统的研究进展[J].遗传, 2015, 9:873-884.
[5] Metz-Boutigue MH, Jollès J, Mazurier J, et al. Human lactotransferrin:amino acid sequence and structural comparisons with other transferrins[J]. Eur J Biochem, 1984, 145(3):659-676.
[6] Bezault J, Bhimani R, Wiprovnick J, et al. Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice[J]. Cancer Res, 1994, 54(9):2310-2312.
[7] Weinberg ED. Human lactoferrin:a novel therapeutic with broad spectrum potential[J]. J Pharm Pharmacol, 2001, 53(10):1303-1310.
[8]曹阳,包永明,安利佳,等.乳铁蛋白研究现状[J].食品科学, 2002,23(12):132-138.
[9] Nagasako Y, Saito H, Tamura Y, et al. Iron-binding properties of bovine lactoferrin in iron-rich solution[J]. J Dairy Sci, 1993, 76(7):1876-1881.
[10] Mata L, Sánchez L, Headon DR, et al. Thermal denaturation of human lactoferrin and its effecton the ability to bind iron[J]. J Agric Food Chem, 1998, 46(10):3964-3970.
[11] Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics[J]. Science, 2002,297(5580):353-356.
[12]徐东芳.地塞米松促进β-淀粉样蛋白的神经元毒性及其机理研究[D].合肥:安徽医科大学, 2007.
[13]李开荣.β淀粉样蛋白25-35对大鼠神经干细胞的毒性和雌激素的保护作用[D].郑州:郑州大学, 2003.
[14] Chuang G, Zhaohui Y, Shuai Z, et al. Intranasal lactoferrin enhancesα-secretase-dependent amyloid precursor protein processing via the ERK1/2-CREB and HIF-1αpathways in an Alzheimer's disease mouse model[J]. Neuropsychopharmacology, 2017,(42):2504-2515.
[15] Martorell P, Llopis S, Gonzalez N, et al. A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan,and reduces amyloidβpeptide toxicity in Caenorhabditis elegans[J].Food Sci Nutr, 2017, 5(2):255-265.
[16] Guoyao W, Yunzhong F, Sheng Y, et al. Glutathione metabolism and its implications for health[J]. Nutrition, 2004, 134(3):489-492.
[17]毕明霞.小胶质细胞乳铁蛋白的表达及其对腹侧中脑神经元的作用研究[D].青岛:青岛大学, 2014.
[18] Fillebeen C, Mitchell V, Dexter D, et al. Lactoferrin is synthesized by mouse brain tissue and its expression is enhanced after MPTP treatment[J]. Brain Res Mol Brain Res, 1999, 72(2):183-194.
[19] Maneva A, Taleva B, Maneva L. Lactoferrin-protector against oxidative stress and regulator of glycolysis in human erythrocytes[J]. Z Naturforsch C, 2003, 58(3-4):256-262.
[20] Safaeian L, Zabolian H. Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat[J]. ISRN Pharmacol,2014, 2014:943523.
[21] Ferriero DM. Neonatal brain injury[J]. N Engl J Med, 2004, 351(4):1985-1995.
[22] Vogel HJ. Lactoferrin, a bird’s eye view[J]. Biochem Cell Biol,2012, 90(3):233-244.
[23] Granic I, Dolga AM, Nijholt IM, et al. InfIammation and NF-kappaB in Alzheimer’s disease and diabetes[J]. J Alzheimers Dis, 2009, 16(4):809-821.
[24] Pan XD, Zhu YG, Lin N, et al. Microglial phagocytosis induced by fibrillar beta-amyloid is attenuated by oligomeric beta-amyloid:implications for Alzheimer's disease[J]. Mol Neurodegener, 2011, 6:45.
[25] Madi NM, El-Saka MH. The possible protective effect of lactoferrin on lipopolysaccharide-induced memory impairment in albino rats[J].Alex J Med, 2018, 54(3):189-286.
[26] Ando K, Hasegawa K, Shindo K, et al. Human lactoferrin activates NF-kB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaceharide-stimulated TLR4 signaling[J]. FEBS J,2010, 277(9):2051-2066.
[27] Xin Z, Deguang S, Tenghao W, et al. LFP-20, a porcine lactoferrin peptide, ameliorates LPS-induced inflammation via the My D88/NF-κB and MyD88/MAPK signaling pathways[J]. Dev Comp lmmunol,2015, 52(2):123-131.
[28]郭婧.牛乳铁蛋白对大鼠小肠空肠上皮细胞株的影响研究[D].广州:南方医科大学, 2016.
[29] Elass E, Masson M, Mazurier J, et al. Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binging ability of interleukin-8 in human endothelial cells[J]. Infect Immunity,2002, 70(4):1860-1866.
[30]黄志华,李良东,韩立民.染料木素的脑保护作用及机制研究进展[J].中国药理学与毒理学杂志, 2015, 29(1):141-146.
[31]王玉梅,刘永平,曹凯,等.黄芩茎叶黄酮对大鼠缺血性记忆障碍和神经炎症的作用[J].中国药理学与毒理学杂志, 2011, 25(2):135-140.
[32] vande Looij Y, Ginet V, Chatagner A, et al. Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain[J]. Ann Clin Transl Neurol, 2014, 1(12):955-967.
[33] Jianhua X, Liming H, Linggang W. Role of Ca2+channels in short-term synaptic plasticity[J]. Curr Opin Neurobiol, 2007, 17(3):352-359.
[34]孙芳玲,王文,张兰,等.钙信号与神经退行性疾病[J].中国康复理论实践, 2013, 19(10):931-935.
[35] Rousseau E, Patrick P, Michel, et al. The iron-binding protein Lactoferrin protects vulnerable dopamine neurons from degeneration by preserving mitochondrial calcium homeostasis[J]. Mol Pharmacol,2013, 84:888-898.
[36]刘明月.基于CREB-BDNF信号转导通路研究开心散及其主要成分3,6’-二芥子酰基蔗糖促神经保护和抗抑郁的作用机制[D].张家口:河北北方学院, 2013.
[37] Chen Y, Zheng Z, Zhu X, et al. Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation[J]. Mol Neurobiol,2015, 52(1):256-269.
[38] Zhao L, Liu X, Liang J, et al. Phosphorylation of p38 MAPK mediates hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury via mitochondria translocation of Bcl-xL in mice[J]. Brain Res, 2013, 1503:78-88.
[39] Meng L, Fengjiao F, Pujie S, et al. Lactoferrin promotes MC3T3-E1osteoblast cells proliferation via MAPK signaling pathways[J]. Int J Biol Macromol, 2018, 107(Part A):137-143.
[2] Vorland LH. Lactoferrin:a multifunctional glycoprotein[J]. APMIS,1999, 107(11):971-981.
[3] Lian-da Q, Fan-ze P, Xi-lin H, et al. Minireview of Lactoferrin research in domestic and overseas[J]. Heilongjiang August First Land Reclamation University, 2005, 17(6):50-54.
[4]庞晓楠,弘笑,魏璇,等.乳铁蛋白的理化性质及其重组表达系统的研究进展[J].遗传, 2015, 9:873-884.
[5] Metz-Boutigue MH, Jollès J, Mazurier J, et al. Human lactotransferrin:amino acid sequence and structural comparisons with other transferrins[J]. Eur J Biochem, 1984, 145(3):659-676.
[6] Bezault J, Bhimani R, Wiprovnick J, et al. Human lactoferrin inhibits growth of solid tumors and development of experimental metastases in mice[J]. Cancer Res, 1994, 54(9):2310-2312.
[7] Weinberg ED. Human lactoferrin:a novel therapeutic with broad spectrum potential[J]. J Pharm Pharmacol, 2001, 53(10):1303-1310.
[8]曹阳,包永明,安利佳,等.乳铁蛋白研究现状[J].食品科学, 2002,23(12):132-138.
[9] Nagasako Y, Saito H, Tamura Y, et al. Iron-binding properties of bovine lactoferrin in iron-rich solution[J]. J Dairy Sci, 1993, 76(7):1876-1881.
[10] Mata L, Sánchez L, Headon DR, et al. Thermal denaturation of human lactoferrin and its effecton the ability to bind iron[J]. J Agric Food Chem, 1998, 46(10):3964-3970.
[11] Hardy J, Selkoe DJ. The amyloid hypothesis of Alzheimer's disease:progress and problems on the road to therapeutics[J]. Science, 2002,297(5580):353-356.
[12]徐东芳.地塞米松促进β-淀粉样蛋白的神经元毒性及其机理研究[D].合肥:安徽医科大学, 2007.
[13]李开荣.β淀粉样蛋白25-35对大鼠神经干细胞的毒性和雌激素的保护作用[D].郑州:郑州大学, 2003.
[14] Chuang G, Zhaohui Y, Shuai Z, et al. Intranasal lactoferrin enhancesα-secretase-dependent amyloid precursor protein processing via the ERK1/2-CREB and HIF-1αpathways in an Alzheimer's disease mouse model[J]. Neuropsychopharmacology, 2017,(42):2504-2515.
[15] Martorell P, Llopis S, Gonzalez N, et al. A nutritional supplement containing lactoferrin stimulates the immune system, extends lifespan,and reduces amyloidβpeptide toxicity in Caenorhabditis elegans[J].Food Sci Nutr, 2017, 5(2):255-265.
[16] Guoyao W, Yunzhong F, Sheng Y, et al. Glutathione metabolism and its implications for health[J]. Nutrition, 2004, 134(3):489-492.
[17]毕明霞.小胶质细胞乳铁蛋白的表达及其对腹侧中脑神经元的作用研究[D].青岛:青岛大学, 2014.
[18] Fillebeen C, Mitchell V, Dexter D, et al. Lactoferrin is synthesized by mouse brain tissue and its expression is enhanced after MPTP treatment[J]. Brain Res Mol Brain Res, 1999, 72(2):183-194.
[19] Maneva A, Taleva B, Maneva L. Lactoferrin-protector against oxidative stress and regulator of glycolysis in human erythrocytes[J]. Z Naturforsch C, 2003, 58(3-4):256-262.
[20] Safaeian L, Zabolian H. Antioxidant effects of bovine lactoferrin on dexamethasone-induced hypertension in rat[J]. ISRN Pharmacol,2014, 2014:943523.
[21] Ferriero DM. Neonatal brain injury[J]. N Engl J Med, 2004, 351(4):1985-1995.
[22] Vogel HJ. Lactoferrin, a bird’s eye view[J]. Biochem Cell Biol,2012, 90(3):233-244.
[23] Granic I, Dolga AM, Nijholt IM, et al. InfIammation and NF-kappaB in Alzheimer’s disease and diabetes[J]. J Alzheimers Dis, 2009, 16(4):809-821.
[24] Pan XD, Zhu YG, Lin N, et al. Microglial phagocytosis induced by fibrillar beta-amyloid is attenuated by oligomeric beta-amyloid:implications for Alzheimer's disease[J]. Mol Neurodegener, 2011, 6:45.
[25] Madi NM, El-Saka MH. The possible protective effect of lactoferrin on lipopolysaccharide-induced memory impairment in albino rats[J].Alex J Med, 2018, 54(3):189-286.
[26] Ando K, Hasegawa K, Shindo K, et al. Human lactoferrin activates NF-kB through the Toll-like receptor 4 pathway while it interferes with the lipopolysaceharide-stimulated TLR4 signaling[J]. FEBS J,2010, 277(9):2051-2066.
[27] Xin Z, Deguang S, Tenghao W, et al. LFP-20, a porcine lactoferrin peptide, ameliorates LPS-induced inflammation via the My D88/NF-κB and MyD88/MAPK signaling pathways[J]. Dev Comp lmmunol,2015, 52(2):123-131.
[28]郭婧.牛乳铁蛋白对大鼠小肠空肠上皮细胞株的影响研究[D].广州:南方医科大学, 2016.
[29] Elass E, Masson M, Mazurier J, et al. Lactoferrin inhibits the lipopolysaccharide-induced expression and proteoglycan-binging ability of interleukin-8 in human endothelial cells[J]. Infect Immunity,2002, 70(4):1860-1866.
[30]黄志华,李良东,韩立民.染料木素的脑保护作用及机制研究进展[J].中国药理学与毒理学杂志, 2015, 29(1):141-146.
[31]王玉梅,刘永平,曹凯,等.黄芩茎叶黄酮对大鼠缺血性记忆障碍和神经炎症的作用[J].中国药理学与毒理学杂志, 2011, 25(2):135-140.
[32] vande Looij Y, Ginet V, Chatagner A, et al. Lactoferrin during lactation protects the immature hypoxic-ischemic rat brain[J]. Ann Clin Transl Neurol, 2014, 1(12):955-967.
[33] Jianhua X, Liming H, Linggang W. Role of Ca2+channels in short-term synaptic plasticity[J]. Curr Opin Neurobiol, 2007, 17(3):352-359.
[34]孙芳玲,王文,张兰,等.钙信号与神经退行性疾病[J].中国康复理论实践, 2013, 19(10):931-935.
[35] Rousseau E, Patrick P, Michel, et al. The iron-binding protein Lactoferrin protects vulnerable dopamine neurons from degeneration by preserving mitochondrial calcium homeostasis[J]. Mol Pharmacol,2013, 84:888-898.
[36]刘明月.基于CREB-BDNF信号转导通路研究开心散及其主要成分3,6’-二芥子酰基蔗糖促神经保护和抗抑郁的作用机制[D].张家口:河北北方学院, 2013.
[37] Chen Y, Zheng Z, Zhu X, et al. Lactoferrin promotes early neurodevelopment and cognition in postnatal piglets by upregulating the BDNF signaling pathway and polysialylation[J]. Mol Neurobiol,2015, 52(1):256-269.
[38] Zhao L, Liu X, Liang J, et al. Phosphorylation of p38 MAPK mediates hypoxic preconditioning-induced neuroprotection against cerebral ischemic injury via mitochondria translocation of Bcl-xL in mice[J]. Brain Res, 2013, 1503:78-88.
[39] Meng L, Fengjiao F, Pujie S, et al. Lactoferrin promotes MC3T3-E1osteoblast cells proliferation via MAPK signaling pathways[J]. Int J Biol Macromol, 2018, 107(Part A):137-143.