脱发实验模型及其药物治疗学现状
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摘要
脱发是一种以毛发缺失为特征的疾病,其病理生理机制及毛发再生治疗是当前研究的焦点问题。脱发实验模型的成功复制对脱发病理机制和药物治疗学研究起到关键的推动作用。本文就国内外已经建立的体内脱发动物模型,体外脱发器官模型及其实验治疗学进展作系统综述,方便研究者根据需要选择合适的模型开展实验。
Alopecia is a kind of disease characterized by loss of hair. Pathophysiological mechanism of alopecia and its hair regeneration therapy is the pressing issues of current study. The successful replication of Alopecia experimental model plays a key role in promoting the study of pathological mechanism and pharmacotherapeutics. This review systematically describes the progress in alopecia animal model and in vitro organ model,which have been established at home and abroad. Based upon the aforementioned experimental models,some relevant applications in experimental therapeutics are simultaneously enumerated. Hopefully all these information facilitate the researchers according to the need to select the appropriate model to carry out the experiment.
Alopecia is a kind of disease characterized by loss of hair. Pathophysiological mechanism of alopecia and its hair regeneration therapy is the pressing issues of current study. The successful replication of Alopecia experimental model plays a key role in promoting the study of pathological mechanism and pharmacotherapeutics. This review systematically describes the progress in alopecia animal model and in vitro organ model,which have been established at home and abroad. Based upon the aforementioned experimental models,some relevant applications in experimental therapeutics are simultaneously enumerated. Hopefully all these information facilitate the researchers according to the need to select the appropriate model to carry out the experiment.
引文
[1]马萍萍,郭红卫,史建强,等.斑秃的治疗现状[J].国际皮肤性病学杂志,2014,40(6):352-355.
[2]孙园园,钟江.民族医药治疗斑秃的研究进展[J].中国民族医药杂志,2015,21(12):28-29.
[3]Uno H.Studies of common baldness of the stumptailed macaque.I.Distribution of the hair follicles[J].J Invest Derm,1967,49(3):288-296.
[4]Uno H,Zimbric ML,Albert DM,et al.Effect of latanoprost on hair growth in the bald scalp of the stumptailed macacque:a pilot study[J].Acta Derm Venereol,2002,82(1):7-12.
[5]Sundberg JP,Cordy WR,King LE Jr.Alopecia areata in aging C3H/He J mice[J].J Invest Dermatol,1994,102(6):847-856.
[6]Wikramanayake TC,Alvarez-Connelly E,Simon J,et al.Heat treatment increases the incidence of alopecia areata in the C3H/He J mouse model[J].Cell Stress Chaperones,2010,15(6):985-991.
[7]Wikramanayake TC,Villasante AC,Mauro LM,et al.Prevention and treatment of alopecia areata with quercetin in the C3H/He J mouse model[J].Cell Stress Chaperones,2012,17(2):267-274.
[8]Xing L,Dai Z,Jabbari A,et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition[J].Nat Med,2014,20(9):1043-1049.
[9]Sun J,Silva KA,Mc Elwee KJ,et al.The C3H/He J mouse and DEBR rat models for alopecia areata:review of preclinical drug screening approaches and results[J].Exp Dermatol,2008,17(10):793-805.
[10]Michie HJ,Jahoda CA,Oliver RF,et al.The DEBR rat:an animal model of human alopecia areata[J].Br J Dermatol,1991,125(2):94-100.
[11]Alli R,Nguyen P,Boyd K,et al.A mouse model of clonal CD+8T lymphocyte-mediated alopecia areata progressing to alopecia universalis[J].J Immunol,2012,188(1):477-486.
[12]铁茹,刘利兵,李旭波,等.硫化钠脱毛剂最佳脱毛浓度的探讨[J].陕西医学杂志,2009,38(10):1283-1284,1303.
[13]李燕梅,黄亚东,曲红艳,等.酸性成纤维细胞生长因子的促细胞增殖作用和对实验秃毛大鼠的疗效研究[J].中国生物工程杂志,2008,28(10):33-38.
[14]李大宁,李梅云,刘进芬,等.表没食子儿茶素没食子酸酯(EGCG)对小鼠脱发模型毛发生长的影响[J].中国美容医学,2010,19(3):350-352.
[15]张春洪.生发酊对C57BL/6小鼠毛发生长作用的实验研究[J].江苏中医药,2012,44(1):74-75.
[16]Jimenez JJ,Yunis AA.Protection from chemotherapyinduced alopecia by 1,25-dihydroxyvitamin D3[J].Cancer Res,1992,52(18):5123-5125.
[17]Paus R,Handjiski B,Eichmüller S,et al.Chemotherapy-induced alopecia in mice.Induction by cyclophosphamide,inhibition by cyclosporine A,and modulation by dexamethasone[J].Am J Pathol,1994,144(4):719-734.
[18]Müller-Rover S,Bulfone-Paus S,Handjiski B,et al.Intercellular adhesion molecule-1 and hair follicle regression[J].J Histochem Cytochem,2000,48(4):557-568.
[19]邢飞,姜波,涂亚庭,等.环磷酰胺对小鼠血清和局部毛囊内ICAM-1及ELAM-1水平的影响[J].中国皮肤性病学杂志,2010,24(4):314-317.
[20]Bichsel KJ,Gogia N,Malouff T,et al.Role for the epidermal growth factor receptor in chemotherapy-induced alopecia[J].PLo S One,2013,8(7):e69368.
[21]Paik SH,Yoon JS,Ryu HH,et al.Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapyinduced alopecia[J].Exp Dermatol,2013,22(7):496-499.
[22]Katikaneni R,Ponnapakkam T,Matsushita O,et al.Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD,a collagen-targeted parathyroid hormone analog,in a non-depilated mouse model[J].Anticancer Drugs,2014,25(1):30-38.
[23]Katikaneni R,Ponnapakkam T,Seymour A,et al.Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner[J].Anticancer Drugs,2014,25(7):819-825.
[24]Nasr Z,Dow LE,Paquet M,et al.Suppression of eukaryotic initiation factor 4E prevents chemotherapy-induced alopecia[J].BMC Pharmacol Toxicol,2013,14:58.
[25]D'Agostini F,Fiallo P,Ghio M,et al.Chemoprevention of doxorubicin-induced alopecia in mice by dietary administration of L-cystine and vitamin B6[J].Arch Dermatol Res,2013,305(1):25-34.
[26]Mc Elwee KJ,Silva K,Beamer WG,et al.Melanocyte and gonad activity as potential severity modifying factors in C3H/He J mouse alopecia areata[J].Exp Dermatol,2001,10(6):420-429.
[27]Matias JR,Malloy V,Orentreich N.Animal models of androgen-dependent disorders of the pilosebaceous apparatus.1.The androchronogenetic alopecia(AGA)mouse as a model for male-pattern baldness[J].Arch Dermatol Res,1989,281(4):247-253.
[28]Park WS,Lee CH,Lee BG,et al.The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse[J].J Dermatol Sci,2003,31(2):91-98.
[29]Crabtree JS,Kilbourne EJ,Peano BJ,et al.A mouse model of androgenetic alopecia[J].Endocrinology,2010,151(5):2373-2380.
[30]赵党生,李淑霞,赵春霖,等.“止脱灵”对实验性大鼠雄激素的调节及对毛发脱落的影响[J].甘肃中医学院学报,2005,22(1):12-15.
[31]李剑峰,章诗富.咪喹莫特的免疫调节机制及临床应用进展[J].医学综述,2009,15(9):1393-1395.
[32]赵恒光.咪喹莫特诱导C3H/He J小鼠斑秃动物模型的建立及发病机理初步研究[D].重庆医科大学,2007.
[33]赵恒光,李惠.咪喹莫特诱导C3H/He J小鼠脱毛实验动物模型的建立[J].中华皮肤科杂志,2008,41(1):25-28.
[34]杜佳,赵恒光,李惠,等.咪喹莫特诱导多品系小鼠脱毛动物模型的建立[J].重庆医科大学学报,2009,34(3):307-309.
[35]Gilhar A,Kam Y,Assy B,et al.Alopecia areata induced in C3H/He J mice by interferon-gamma:evidence for loss of immune privilege[J].J Invest Dermatol,2005,124(1):288-289.
[36]Gilhar A,Landau M,Assy B,et al.Transfer of alopecia areata in the human scalp graft/Prkdc(scid)(SCID)mouse system is characterized by a TH1 response[J].Clin Immunol,2003,106(3):181-187.
[37]Ryu S,Lee Y,Hyun MY,et al.Mycophenolate antagonizes IFN-γ-induced catagen-like changes viaβ-catenin activation in human dermal papilla cells and hair follicles[J].Int J Mol Sci,2014,15(9):16800-16815.
[38]Mc Elwee KJ,Boggess D,King LE Jr,et al.Experimental induction of alopecia areata-like hair loss in C3H/He J mice using full-thickness skin grafts[J].J Invest Dermatol,1998,111(5):797-803.
[39]Freyschmidt-Paul P,Mc Elwee KJ,Hoffmann R,et al.Interferon-gamma-deficient mice are resistant to the development of alopecia areata[J].Br J Dermatol,2006,155(3):515-521.
[40]Mc Elwee KJ,Niiyama S,Freyschmidt-Paul P,et al.Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/He J mice[J].Exp Dermatol,2003,12(1):30-36.
[41]Philpott MP,Green MR,Kealey T.Human hair growth in vitro[J].J Cell Sci,1990,97(Pt3):463-471.
[42]李宇飞,张瑛,赵建宁,等.Williams E培养基中人游离毛囊器官培养的观测[J].中国医师杂志,2013,15(9):1166-1169.
[43]许成蓉,陈兴平,李文刚,等.HGF和TGF-β在拉坦前列素促毛发生长中的作用[J].中国麻风皮肤病杂志,2007,23(10):865-866.
[44]吴贤杰,郑敏,吕中法,等.阿糖胞苷引起毛囊损伤离体模型的建立以及他克莫司对其的逆转作用[J].中国现代应用药学,2005,22(2):109-113.
[2]孙园园,钟江.民族医药治疗斑秃的研究进展[J].中国民族医药杂志,2015,21(12):28-29.
[3]Uno H.Studies of common baldness of the stumptailed macaque.I.Distribution of the hair follicles[J].J Invest Derm,1967,49(3):288-296.
[4]Uno H,Zimbric ML,Albert DM,et al.Effect of latanoprost on hair growth in the bald scalp of the stumptailed macacque:a pilot study[J].Acta Derm Venereol,2002,82(1):7-12.
[5]Sundberg JP,Cordy WR,King LE Jr.Alopecia areata in aging C3H/He J mice[J].J Invest Dermatol,1994,102(6):847-856.
[6]Wikramanayake TC,Alvarez-Connelly E,Simon J,et al.Heat treatment increases the incidence of alopecia areata in the C3H/He J mouse model[J].Cell Stress Chaperones,2010,15(6):985-991.
[7]Wikramanayake TC,Villasante AC,Mauro LM,et al.Prevention and treatment of alopecia areata with quercetin in the C3H/He J mouse model[J].Cell Stress Chaperones,2012,17(2):267-274.
[8]Xing L,Dai Z,Jabbari A,et al.Alopecia areata is driven by cytotoxic T lymphocytes and is reversed by JAK inhibition[J].Nat Med,2014,20(9):1043-1049.
[9]Sun J,Silva KA,Mc Elwee KJ,et al.The C3H/He J mouse and DEBR rat models for alopecia areata:review of preclinical drug screening approaches and results[J].Exp Dermatol,2008,17(10):793-805.
[10]Michie HJ,Jahoda CA,Oliver RF,et al.The DEBR rat:an animal model of human alopecia areata[J].Br J Dermatol,1991,125(2):94-100.
[11]Alli R,Nguyen P,Boyd K,et al.A mouse model of clonal CD+8T lymphocyte-mediated alopecia areata progressing to alopecia universalis[J].J Immunol,2012,188(1):477-486.
[12]铁茹,刘利兵,李旭波,等.硫化钠脱毛剂最佳脱毛浓度的探讨[J].陕西医学杂志,2009,38(10):1283-1284,1303.
[13]李燕梅,黄亚东,曲红艳,等.酸性成纤维细胞生长因子的促细胞增殖作用和对实验秃毛大鼠的疗效研究[J].中国生物工程杂志,2008,28(10):33-38.
[14]李大宁,李梅云,刘进芬,等.表没食子儿茶素没食子酸酯(EGCG)对小鼠脱发模型毛发生长的影响[J].中国美容医学,2010,19(3):350-352.
[15]张春洪.生发酊对C57BL/6小鼠毛发生长作用的实验研究[J].江苏中医药,2012,44(1):74-75.
[16]Jimenez JJ,Yunis AA.Protection from chemotherapyinduced alopecia by 1,25-dihydroxyvitamin D3[J].Cancer Res,1992,52(18):5123-5125.
[17]Paus R,Handjiski B,Eichmüller S,et al.Chemotherapy-induced alopecia in mice.Induction by cyclophosphamide,inhibition by cyclosporine A,and modulation by dexamethasone[J].Am J Pathol,1994,144(4):719-734.
[18]Müller-Rover S,Bulfone-Paus S,Handjiski B,et al.Intercellular adhesion molecule-1 and hair follicle regression[J].J Histochem Cytochem,2000,48(4):557-568.
[19]邢飞,姜波,涂亚庭,等.环磷酰胺对小鼠血清和局部毛囊内ICAM-1及ELAM-1水平的影响[J].中国皮肤性病学杂志,2010,24(4):314-317.
[20]Bichsel KJ,Gogia N,Malouff T,et al.Role for the epidermal growth factor receptor in chemotherapy-induced alopecia[J].PLo S One,2013,8(7):e69368.
[21]Paik SH,Yoon JS,Ryu HH,et al.Pretreatment of epidermal growth factor promotes primary hair recovery via the dystrophic anagen pathway after chemotherapyinduced alopecia[J].Exp Dermatol,2013,22(7):496-499.
[22]Katikaneni R,Ponnapakkam T,Matsushita O,et al.Treatment and prevention of chemotherapy-induced alopecia with PTH-CBD,a collagen-targeted parathyroid hormone analog,in a non-depilated mouse model[J].Anticancer Drugs,2014,25(1):30-38.
[23]Katikaneni R,Ponnapakkam T,Seymour A,et al.Parathyroid hormone linked to a collagen binding domain promotes hair growth in a mouse model of chemotherapy-induced alopecia in a dose-dependent manner[J].Anticancer Drugs,2014,25(7):819-825.
[24]Nasr Z,Dow LE,Paquet M,et al.Suppression of eukaryotic initiation factor 4E prevents chemotherapy-induced alopecia[J].BMC Pharmacol Toxicol,2013,14:58.
[25]D'Agostini F,Fiallo P,Ghio M,et al.Chemoprevention of doxorubicin-induced alopecia in mice by dietary administration of L-cystine and vitamin B6[J].Arch Dermatol Res,2013,305(1):25-34.
[26]Mc Elwee KJ,Silva K,Beamer WG,et al.Melanocyte and gonad activity as potential severity modifying factors in C3H/He J mouse alopecia areata[J].Exp Dermatol,2001,10(6):420-429.
[27]Matias JR,Malloy V,Orentreich N.Animal models of androgen-dependent disorders of the pilosebaceous apparatus.1.The androchronogenetic alopecia(AGA)mouse as a model for male-pattern baldness[J].Arch Dermatol Res,1989,281(4):247-253.
[28]Park WS,Lee CH,Lee BG,et al.The extract of Thujae occidentalis semen inhibited 5alpha-reductase and androchronogenetic alopecia of B6CBAF1/j hybrid mouse[J].J Dermatol Sci,2003,31(2):91-98.
[29]Crabtree JS,Kilbourne EJ,Peano BJ,et al.A mouse model of androgenetic alopecia[J].Endocrinology,2010,151(5):2373-2380.
[30]赵党生,李淑霞,赵春霖,等.“止脱灵”对实验性大鼠雄激素的调节及对毛发脱落的影响[J].甘肃中医学院学报,2005,22(1):12-15.
[31]李剑峰,章诗富.咪喹莫特的免疫调节机制及临床应用进展[J].医学综述,2009,15(9):1393-1395.
[32]赵恒光.咪喹莫特诱导C3H/He J小鼠斑秃动物模型的建立及发病机理初步研究[D].重庆医科大学,2007.
[33]赵恒光,李惠.咪喹莫特诱导C3H/He J小鼠脱毛实验动物模型的建立[J].中华皮肤科杂志,2008,41(1):25-28.
[34]杜佳,赵恒光,李惠,等.咪喹莫特诱导多品系小鼠脱毛动物模型的建立[J].重庆医科大学学报,2009,34(3):307-309.
[35]Gilhar A,Kam Y,Assy B,et al.Alopecia areata induced in C3H/He J mice by interferon-gamma:evidence for loss of immune privilege[J].J Invest Dermatol,2005,124(1):288-289.
[36]Gilhar A,Landau M,Assy B,et al.Transfer of alopecia areata in the human scalp graft/Prkdc(scid)(SCID)mouse system is characterized by a TH1 response[J].Clin Immunol,2003,106(3):181-187.
[37]Ryu S,Lee Y,Hyun MY,et al.Mycophenolate antagonizes IFN-γ-induced catagen-like changes viaβ-catenin activation in human dermal papilla cells and hair follicles[J].Int J Mol Sci,2014,15(9):16800-16815.
[38]Mc Elwee KJ,Boggess D,King LE Jr,et al.Experimental induction of alopecia areata-like hair loss in C3H/He J mice using full-thickness skin grafts[J].J Invest Dermatol,1998,111(5):797-803.
[39]Freyschmidt-Paul P,Mc Elwee KJ,Hoffmann R,et al.Interferon-gamma-deficient mice are resistant to the development of alopecia areata[J].Br J Dermatol,2006,155(3):515-521.
[40]Mc Elwee KJ,Niiyama S,Freyschmidt-Paul P,et al.Dietary soy oil content and soy-derived phytoestrogen genistein increase resistance to alopecia areata onset in C3H/He J mice[J].Exp Dermatol,2003,12(1):30-36.
[41]Philpott MP,Green MR,Kealey T.Human hair growth in vitro[J].J Cell Sci,1990,97(Pt3):463-471.
[42]李宇飞,张瑛,赵建宁,等.Williams E培养基中人游离毛囊器官培养的观测[J].中国医师杂志,2013,15(9):1166-1169.
[43]许成蓉,陈兴平,李文刚,等.HGF和TGF-β在拉坦前列素促毛发生长中的作用[J].中国麻风皮肤病杂志,2007,23(10):865-866.
[44]吴贤杰,郑敏,吕中法,等.阿糖胞苷引起毛囊损伤离体模型的建立以及他克莫司对其的逆转作用[J].中国现代应用药学,2005,22(2):109-113.