半合成四环素类抗生素在多发性硬化中的应用研究进展
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摘要
半合成四环素类抗生素是一种四环素的衍生物,现在的研究显示其除了具有抑菌、控制炎症反应的抗生素活性外,还具有非抗生素活性包括抗凋亡和抗氧化作用。临床已将其作为神经保护剂应用于脑卒中、多发性硬化等多种急慢性神经系统疾病的治疗中。本文主要针对半合成四环素类抗生素(米诺环素和多西环素)治疗MS的机制做一综述。
The semi-synthetic tetracycline antibiotic is a tetracycline derivative.The present study has shown that aside from its antibiotic activities(bacteriostatic and anti-inflammatory effect),it also has non-antibiotic activities,including anti-oxidation and anti-apoptosis properties.In clinical it has been served as a neuroprotective agent for the treatment of stroke,multiple sclerosis and other acute and chronic neurological diseases.In this paper,the mechanism of semi-synthetic tetracycline antibiotics(minocycline and doxycycline) treating multiple sclerosis will be mainly reviewed.
The semi-synthetic tetracycline antibiotic is a tetracycline derivative.The present study has shown that aside from its antibiotic activities(bacteriostatic and anti-inflammatory effect),it also has non-antibiotic activities,including anti-oxidation and anti-apoptosis properties.In clinical it has been served as a neuroprotective agent for the treatment of stroke,multiple sclerosis and other acute and chronic neurological diseases.In this paper,the mechanism of semi-synthetic tetracycline antibiotics(minocycline and doxycycline) treating multiple sclerosis will be mainly reviewed.
引文
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2张先龙,唐玉兰,肖凯文,等.多发性硬化患者合并症临床分析[J].中国全科医学,2011,14(7):2306.
3 Popovic N,Schubart A,Goetz BD,et al.Inhibition of autoimmune encephalomyelitis bya tetracycline[J].Ann Neurol,2002,51(2):215-223.
4 Parks WC,Wilson CL,López-Boado YS.Matrix metalloproteinases as modulators of in-flammation and innate immunity[J].NatRev Immunol,2004,4(8):617-629.
5 Pourtaghi N,Radvar M,Mooney J,et al.The effect of subgingival antimicrobial therapyon the levels of stromelysin and tissue inhibitorof metalloproteinases in gingival crevicular flu-id[J].J Periodontol,1996,67(9):866-870.
6 Rasmussen S,Imitola J,Ayuso-Sacido A,et al.Reversible neural stem cell niche dys-function in a modle of multiple sclerosis[J].Ann Neurol,2011,69(5):878-891.
7张贺,肖波,杨欢,等.p38MAPK蛋白在米诺环素抑制小鼠EAE发病中的表达变化及意义[J].医学临床研究,2008,25(9):1556-1559.
8 Wei Hu,Metselaar J,Li-Hong Ben,et al.PEG mioncycline-liposomes ameliorate CNSautoimmune disease[J].PLoS ONE,2009,4(1):41-51.
9 Defaux A,Zurich MG,Honegger P,et al.Minocycline promotes remyelination in aggrega-ting rat brain cell cultures after interferon-γplus lipopolysaccharide-induced demyelina-tion[J].Neuroscience,2011,187:84-92.
10 Chen X,Ma L,Jiang Y,et al.Minocy-cline up-regulates the expression of brain-derived neurotrophic factor and nerve growth factor in experimental autoimmune encephalo-myelitis[J].Eur J Pharmacol,2012,686(1/2/3):124-129.
11 Yong VW,Power C,Forsyth P,et al.Metalloproteinases in biology and pathology of the nervous system[J].Nat Rev Neu-rosci,2001,2(7):502-511.
12 Popovic N,Schubart A,Goetz BD,et al.Inhibition of autoimmune encephalomyelitis by a tetracycline[J].Ann Neurol,2002,51(2):215-223.
13李佩琼,王九辉,曾祥周,等.中国男性健康志愿者单剂量用盐酸多西环素的药代动力学研究[J].海南医学院学报,2009,15(9):1044-1047.
14 Omari KM,Lutz SE,Santambrogio L,et al.Neuroprotection and remyelination after auto-1immune demyelination in mice that inducibly overexpress CXCL1[J].Am J Pathol,2009,174(1):164-176.
15 Jantzie LL,Cheung PY,Todd KG,et al.Doxycycline reduces cleaved caspase-3 and microglial activation in an animal model of neonatal hypoxia-ischemia[J].J Cereb Blood Flow Metab,2005,25(3):314-324.
2张先龙,唐玉兰,肖凯文,等.多发性硬化患者合并症临床分析[J].中国全科医学,2011,14(7):2306.
3 Popovic N,Schubart A,Goetz BD,et al.Inhibition of autoimmune encephalomyelitis bya tetracycline[J].Ann Neurol,2002,51(2):215-223.
4 Parks WC,Wilson CL,López-Boado YS.Matrix metalloproteinases as modulators of in-flammation and innate immunity[J].NatRev Immunol,2004,4(8):617-629.
5 Pourtaghi N,Radvar M,Mooney J,et al.The effect of subgingival antimicrobial therapyon the levels of stromelysin and tissue inhibitorof metalloproteinases in gingival crevicular flu-id[J].J Periodontol,1996,67(9):866-870.
6 Rasmussen S,Imitola J,Ayuso-Sacido A,et al.Reversible neural stem cell niche dys-function in a modle of multiple sclerosis[J].Ann Neurol,2011,69(5):878-891.
7张贺,肖波,杨欢,等.p38MAPK蛋白在米诺环素抑制小鼠EAE发病中的表达变化及意义[J].医学临床研究,2008,25(9):1556-1559.
8 Wei Hu,Metselaar J,Li-Hong Ben,et al.PEG mioncycline-liposomes ameliorate CNSautoimmune disease[J].PLoS ONE,2009,4(1):41-51.
9 Defaux A,Zurich MG,Honegger P,et al.Minocycline promotes remyelination in aggrega-ting rat brain cell cultures after interferon-γplus lipopolysaccharide-induced demyelina-tion[J].Neuroscience,2011,187:84-92.
10 Chen X,Ma L,Jiang Y,et al.Minocy-cline up-regulates the expression of brain-derived neurotrophic factor and nerve growth factor in experimental autoimmune encephalo-myelitis[J].Eur J Pharmacol,2012,686(1/2/3):124-129.
11 Yong VW,Power C,Forsyth P,et al.Metalloproteinases in biology and pathology of the nervous system[J].Nat Rev Neu-rosci,2001,2(7):502-511.
12 Popovic N,Schubart A,Goetz BD,et al.Inhibition of autoimmune encephalomyelitis by a tetracycline[J].Ann Neurol,2002,51(2):215-223.
13李佩琼,王九辉,曾祥周,等.中国男性健康志愿者单剂量用盐酸多西环素的药代动力学研究[J].海南医学院学报,2009,15(9):1044-1047.
14 Omari KM,Lutz SE,Santambrogio L,et al.Neuroprotection and remyelination after auto-1immune demyelination in mice that inducibly overexpress CXCL1[J].Am J Pathol,2009,174(1):164-176.
15 Jantzie LL,Cheung PY,Todd KG,et al.Doxycycline reduces cleaved caspase-3 and microglial activation in an animal model of neonatal hypoxia-ischemia[J].J Cereb Blood Flow Metab,2005,25(3):314-324.