瘦素抗体对兔耳增生性瘢痕TGF-β～1mRNA表达的影响
|
摘要
目的：探讨瘦素抗体对兔耳增生性瘢痕TGF-β1mRNA表达的影响。
方法：新西兰大白兔25只,在双侧兔耳腹侧分别制备直径为0.7cm,深达软骨膜的圆形切口3个,共获得瘢痕模型150个。随机分为5组：对照组(盐水组)、实验组1(高浓度瘦素抗体外用组/1：50倍稀释)、实验组2(低浓度瘦素抗体外用组/1：100倍稀释)、实验组3(高浓度瘦素抗体外用+注射组)、实验组4(低浓度瘦素抗体外用+注射组)。于模型形成当日起每日局部外用相应试剂(共14天),后两组于瘢痕形成以后开始每周注射一次相应试剂,共3次,术后第40天所有标本取材,测量瘢痕增生指数、组织病理、并分别测量TGF-β1mRNA的表达量。
结果：瘦素抗体组与盐水组相比较TGF-β1mRNA的表达量均下降。其中对照组与高浓度瘦素抗体外用组(P<0.05)和与高浓度瘦素抗体外用+注射组(P<0.05)有明显统计学差异,实验组间无统计学差异。
结论：兔耳增生性瘢痕模型形成以后每日局部外用瘦素抗体2次可以减少增生性瘢痕的形成,且高浓度组对TGF-β1mRNA表达的抑制作用更明显,但瘢痕形成以后局部注射并未起到更加抑制瘢痕增生的效果。
Objective:The paper is aimed at probing into Anti-Leptin's effects on rabbit ear hypertrophic scar expression of TGF-β1mRNA
Methods:In this investigation,25 white New Zealand rabbits are prepared, with 3 scar models from either side of rabbit ears, thus,150 models in total. Each scar model is a circular incision with the diameter of 0.7 cm taken from the ventral deep to perichondrium. They are divided into 5 groups at random;①control group (brine/saline group)②E group 1(high concentration of leptin antibody external groups/1:50 dilution)③E group 2(low concentration of leptin antibody external groups/1:100 dilution)④E group 3(high concentration of leptin antibody external+injection group)⑤E group 4(low concentration of leptin antibody external+injection group)
After the formation of the models, topical application was given every day, lasting 14 days. When the scars were formed, the latter two groups began to inject the corresponding reagents once a week,3 times in total. On the 40th day, all the samples were prepared to measure Hypertrophic Index, histopathology, and used to measure the expression of TGF-β1mRNA.
Results:Compared with the saline group, Leptin antibody group the expression of TGF-β1mRNA volume decreased. Among five groups, there are statistically significant differences.between control group and E group 1 (high concentration of leptin antibody external groups P<0.05) and E group 3(high concentration of leptin antibody external+injection group P<0.05), while there is no such differences between E groups.
Conclusion:After the formation of the rabbit ear model of hypertrophic scar, topical application twice a day can reduce the leptin antibody, and inhibition of high concentrations against the expression of TGF-β1mRNA was more obvious, but it did not play a more inhibitory effect after the formation of scar.
方法：新西兰大白兔25只,在双侧兔耳腹侧分别制备直径为0.7cm,深达软骨膜的圆形切口3个,共获得瘢痕模型150个。随机分为5组：对照组(盐水组)、实验组1(高浓度瘦素抗体外用组/1：50倍稀释)、实验组2(低浓度瘦素抗体外用组/1：100倍稀释)、实验组3(高浓度瘦素抗体外用+注射组)、实验组4(低浓度瘦素抗体外用+注射组)。于模型形成当日起每日局部外用相应试剂(共14天),后两组于瘢痕形成以后开始每周注射一次相应试剂,共3次,术后第40天所有标本取材,测量瘢痕增生指数、组织病理、并分别测量TGF-β1mRNA的表达量。
结果：瘦素抗体组与盐水组相比较TGF-β1mRNA的表达量均下降。其中对照组与高浓度瘦素抗体外用组(P<0.05)和与高浓度瘦素抗体外用+注射组(P<0.05)有明显统计学差异,实验组间无统计学差异。
结论：兔耳增生性瘢痕模型形成以后每日局部外用瘦素抗体2次可以减少增生性瘢痕的形成,且高浓度组对TGF-β1mRNA表达的抑制作用更明显,但瘢痕形成以后局部注射并未起到更加抑制瘢痕增生的效果。
Objective:The paper is aimed at probing into Anti-Leptin's effects on rabbit ear hypertrophic scar expression of TGF-β1mRNA
Methods:In this investigation,25 white New Zealand rabbits are prepared, with 3 scar models from either side of rabbit ears, thus,150 models in total. Each scar model is a circular incision with the diameter of 0.7 cm taken from the ventral deep to perichondrium. They are divided into 5 groups at random;①control group (brine/saline group)②E group 1(high concentration of leptin antibody external groups/1:50 dilution)③E group 2(low concentration of leptin antibody external groups/1:100 dilution)④E group 3(high concentration of leptin antibody external+injection group)⑤E group 4(low concentration of leptin antibody external+injection group)
After the formation of the models, topical application was given every day, lasting 14 days. When the scars were formed, the latter two groups began to inject the corresponding reagents once a week,3 times in total. On the 40th day, all the samples were prepared to measure Hypertrophic Index, histopathology, and used to measure the expression of TGF-β1mRNA.
Results:Compared with the saline group, Leptin antibody group the expression of TGF-β1mRNA volume decreased. Among five groups, there are statistically significant differences.between control group and E group 1 (high concentration of leptin antibody external groups P<0.05) and E group 3(high concentration of leptin antibody external+injection group P<0.05), while there is no such differences between E groups.
Conclusion:After the formation of the rabbit ear model of hypertrophic scar, topical application twice a day can reduce the leptin antibody, and inhibition of high concentrations against the expression of TGF-β1mRNA was more obvious, but it did not play a more inhibitory effect after the formation of scar.
引文
[1]Lain QL, Lu L. Role of leptin in immunity. CellMolImmunol.2007,4(1):1-13.
[2]Fietta P. Focus on leptin, a pleiotropic hormone. Minerva Med,2005, 96(2):65-75.
[3]陈伟、付小兵、葛世丽等,增生性瘢痕形成和成熟过程中TGF-β1、TGF-β。受体的基因表达变化.中华整形外科杂志,2004,7(20)：308-309.
[4]Hu M, Sabelman EE, Cao Y, et al. Three-dimensional hyaluronicacid grafts promote healing and reduce scar formation in skin incision wounds. J Biomed Mater Res,2003,67B(1):586.
[5]Cheng CL, Guo JS, Luk J, et al. The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci.2004,74(18):2237-2249.
[6]张选奋、郭树忠、张琳西等.TGF-β1对兔耳创面肉芽组织和瘢痕组织蛋白激酶C活性的影响.中国美容医学.2004,4(13)：140-142.
[7]曾维惠、王倩倩、覃静净、耿松梅、徐磊、聂建军等,ALA-PDT对兔耳增生性瘢痕抑制效应及作用机制的初步研究.中国美容医学2011,20(1):83-86
[8]王惠东,增生性瘢痕与瘢痕疙瘩致病相关基因的研究进展,中国美容医学.2008,17(7)：1098-1100
[9]李伟人、岑瑛、李晓红,病理性瘢痕中丙二醛、黄嘌呤氧化酶和总抗氧化能力的变化.中华整形外科杂志,2007,23(6):526-527
[10]李伟人、岑瑛、刘雪梅等,病理性瘢痕中主要氧化酶和抗氧化酶活性测定.生物学与生物物理进展,2007,34(8)：851-855
[11]刘忠、雷丽华、李旋、黄晓琴、程玉琪、易成刚等,米诺地尔对增生性瘢痕成纤维细胞及超氧化物岐化酶的影响.中国美容医学2009,18(6):826-828
[12]尚任初、夏照帆、杨珺等.成纤维细胞促进真皮替代物血管化的作用机制.中国修复重建外科杂志.2003,17(2)：100-103
[13]COOK H, DAVIES KJ. HARDING KG. et al. Defective extracellular matrix reorganization by chronicwound fibroblasts is assocjated with alterations in TIMP-1,TIMP-2. and MMP-2 activity. J Invest Dermatol,2000,115(2):225-233.
[14]Shi HP, Most D, Efron DT, et al. The role of inos in wound healing. Surgery.2001,130(2):225-229.
[15]Ring BD, Scully S, Davis CR, et al. Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice. Endocrinology.2000,14(1):446-449.
[16]Stallmeyer B, Kampfer H, Podda M, et al. A novel keratinocyte mitogen: regulation of leptin and its functional receptor in skin repair. J Invest Dermatol.2001,117(1):98-105.
[17]李培兵、金宏、刘佃辛等.瘦素促进大鼠皮肤创伤愈合作用的实验研究.中华医学杂志.2003,83(9)：800-802.
[18]Glasow A, Kiess W, Anderegg U, et al. Expression of leptin(ob) and leptin receptor (ob-R) in human fibroblasts:regulation of leptin secretion by insulin. J Clin Endocrinol Metab.2001,86(9):4472-4479.
[19]李培兵、金宏等.瘦素对体外大鼠成纤维细胞增值与胶原合成的影响.Chinese J Reparative and Reconstructive Surgery,2005. Vol 19(1).
[20]蔡紫光,彭旦明.增生陛瘢痕研究进展,实用中西医结合临床2010,10(3)：91-94
[21]赵文鲁、匡瑞霞、刘肃、陈璐等,积雪草甙对兔耳增生性瘢痕TGF-p mRNA表达的影响.中国美容医学2009,18(1):72-75
[22]Saulis AS. Mogford JH. Mustoe TA. Eflfect of M ederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002;110f11:177-183
[23]杨东运,李世荣,李钢,等.人皮肤移植增生性瘢痕裸鼠模型的建立,第三军医大学学报2004,26(10)：899
[24]李希军、柳大烈、王吉慧等.兔耳增生性瘢痕模型建立方法的探讨.中国美容医学.2006,5(15)：499-500.
[25]周勤生、马少林、董祥林等.兔耳增生性瘢痕模型的建立与应用.新疆医 科大报.2005,8(28)：746-748.
[26]李颖、王继华、何永静、杜永贵、刘垠、赵阳等,TNF-a抑制兔耳瘢痕增生的实验研究.中国美容医学2009,18(6):828-831
[27]曾海峰、韩晓霞、刘蓓、鲁开化、郭树忠等,他克莫司抑制兔耳瘢痕增生的作用及其机制研究.中国美容医学2011,20(1):68-70
[28]Tateshita T, Ono I, Kaneko F, et al. Effect of collagen matrix containing transforming growth factor (TGF)-beta (1) on wound contraction. Dermatol Sci 2001,27(2):104-113.
[29]王齐,聂芳菲,赵霞,等.Periostin在过度增生性瘢痕的表达及其与TGF-B1、和受体的相关性.中华整形外科杂志,2007,23(3)：229-232
[30]Fujiwara M, Muragaki Y, Oshima A. Dpregulation of transforminggrowth factor-betal and vascular endothelial growth factor in culturedkeloid fibroblasts:relevance to angiogenic activity. Arch DermatolRes,2005, 297:161-169
[31]王西樵,刘英开,毛志刚,等.增生性瘢痕中成纤维细胞生物学功能变化与微血管病理改变的研究。创伤外科杂志,2007,9(4)：311-314
[32]岳毅刚,蒋常文,李佩英,等.血管内皮生长因子抗体靶向血管治疗对增生性瘢痕工型胶原蛋白表达的影响.中华烧伤杂志,2006,22(6)：427-430
[1]Monica CT, Willem MV. Magda MW. et al. Prevention and curative management of hypertrophic scar formation. Bums,2009,35(4):463-475.
[2]王齐,聂芳菲,赵霞,等.Periostin在过度增生性瘢痕的表达及其与TGF-B1、和受体的相关性.中华整形外科杂志,2007,23(3)：229-232
[3]Fujiwara M, Muragaki Y, Oshima A. Upregulation of transforminggrowth factor-betal and vascular endothelial growth factor in culturedkeloid fibroblasts:relevance to angiogenic activity. Arch DermatolRes,2005, 297:161-169
[4]王西樵,刘英开,毛志刚,等.增生性瘢痕中成纤维细胞生物学功能变化与微血管病理改变的研究。创伤外科杂志,2007,9(4)：311-314
[5]岳毅刚,蒋常文,李佩英,等.血管内皮生长因子抗体靶向血管治疗对增生性瘢痕I型胶原蛋白表达的影响.中华烧伤杂志,2006,22(6):427-430
[6]高明月、蔺洁、张文显.增生性瘢痕的防治现状与展望.中国组织工程研究与临床康复.第14卷第20期2010,5(14):3753-3756
[7]余艳、王玮蓁,成纤维细胞与瘢痕的研究进展.湖北中志.2006,28(2)：55-56
[8]王惠东,增生性瘢痕与瘢痕疙瘩致病相关基因的研究进展,中国美容医学.2008,17(7)：1098-1100
[9]曹毅,郭建辉,陶茂灿,中药制剂对兔耳增生性瘢痕组织的影响.中华中医药学刊.2008,26(1)：96-97
[10]Chemof WG, Cramer H, Stephanie SH. The efficacy of topical silicone gel elastomers in the treatment of hypertrophic scars, keloid sears, and post-laser exfoliation erythema Aesthetic Plast Surg,2007, 31(5):495-500.
[11]Reno F, Sabbatini M, Lombardi F, et al. In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic sears. Wound Repair Regen,2003,11(5):331-336.
[12]Tayfim A, Kaan G, Mi that A. Combination of diferent techniques fortlle treatment of earlobe keloids. Aesth Plast Surg.2002,26:184-188
[13]Atiyeh BS. Nonsurgical management of hypertrophic scars:evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast Surg,2007,31(5):468-492.
[14]Caccialanza M, Piccinno R, Schiem A. Postoperative radiotherapy of keloids:A twenty-year experience. Eur J Derm atol,2002,12:58-62
[15]张振、章一新.增生性瘢痕治疗的研究进展.组织工程与重建外科杂志.2010,6(3)：178-180
[16]Mustoe TA, Cooter RD, Gold MH, etal. International clinical recommendations on scar management. Plast Reconstr Surg,2002, 110(2):560-571.
[17]Bouzari N. Davis SC. Nouri K. Laser treatment of keloids and hypertrophic scars. Int J Dermatol,2007,46(1):80-88.
[18]Kuo YR, Wu WS, Jeng SF, et al. Activation of ERK and p38kinase mediated keloid fibmblast apoptosis after flashlamp pulsed-dye laser treatment. Lasers Surg Med,2005,36(1):31-37.
[19]李惠斌,蔡景龙.瘢痕疙瘩治疗研究进展.中华医学美学美容杂志,2004,10(2)：126
[20]李旋,刘达恩,欧增达等,丹参总酮对体外模拟人增生性瘢痕的作用.中华烧伤杂志,2009,25(1)：62-63
[21]万鲲,高申.旋复花提取物对人增生性瘢痕成纤维细胞抑制作用的研究.中国药物应用与监测,2007,4(6)：29-30,58
[22]赵文鲁、匡瑞霞、刘肃等,积雪草甙对兔耳增生性瘢痕TGF-β1mRNA表达的影响.中国美容医学,2009,18(1)：71-7
[23]蔡紫光,彭旦明.增生陛瘢痕研究进展,实用中西医结合临床2010,10(3)：91-94
[24]Saulis AS. Mogford JH. Mustoe TA. Eflfect of M ederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002,110(1):177-183
[25]杨东运,李世荣,李钢,等.人皮肤移植增生性瘢痕裸鼠模型的建立,第 三军医大学学报2004,26(10)：899
[26]Lain QL, Lu L. Role of leptin in immunity. Cell Mol Immunol。 2007.4(1):1-13.
[27]Fietta P. Focus on leptin, a pleiotropic hormone. Minerva Med,2005, 96(2):65-75.
[28]Banks WA. The many lives of leptin. Peptidest 2004,25(3):331-338.
[29]Lin J. Yan GT。Hao XH. et. al. Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A inperipheral blood and central secretory tissues. World JGastroenterol,2005,11 (7):1000-1004.
[30]Niv-Spector L, Gonen-Berger D, Gourdou I, et al. Identificationof the hydrophobic strand in the A-B loop of leptin as majorbinding site 111: implicarions for large scale preparation of potentrecombinant human and ovine leptin antagonists. Bioehem J,2005,391 (Pt 2)：221-230.
[31]Zieba D. Amatalden M, Williams G. Regulatory roles of leptin inreproduction and metabolism:a comparative review. DomesticAnim Endoerinol,2005,29(1):166-185.
[32]WaelputWt Brouckae#tP, Broekaert. D, et al. A roleforleptininthe systemic inflammatory response syndrome(SIRS)and inimmune response, an 岬date. Curr Med Chem,2006.13(4)-.465-475.
[33]Marikovsky M, Rosenblum el。Faltin Z, et al. Appearance ofleptin in wound fluid " response to injury. Wound RepairRngen,2002,10(5):302-307.
[34]Murad A. Nath AK, Cha ST. et. al. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J,2003t 17(13):1895-1897.
[35]李培兵.金宏.刘佃辛,等.瘦豪对体外大鼠成纤维细胞增殖与胶原台成的影响.中国修复重建外科杂志,2005,19(1):20-22.
[36]张凯、司艺玲、林季等瘦素及其抗体对小鼠皮肤创伤的修复作用标记免疫分析与临床1006-1703(2008)04-0231-03
[37]Glasow A, Kiess W, Anderegg U, et al. Expression of leptin(oB-Rb) in human fibroblasts:regulation of leptin secretion by insulin. J Clin Endocrinol Metab,2001,86(9):4472-4479.
[2]Fietta P. Focus on leptin, a pleiotropic hormone. Minerva Med,2005, 96(2):65-75.
[3]陈伟、付小兵、葛世丽等,增生性瘢痕形成和成熟过程中TGF-β1、TGF-β。受体的基因表达变化.中华整形外科杂志,2004,7(20)：308-309.
[4]Hu M, Sabelman EE, Cao Y, et al. Three-dimensional hyaluronicacid grafts promote healing and reduce scar formation in skin incision wounds. J Biomed Mater Res,2003,67B(1):586.
[5]Cheng CL, Guo JS, Luk J, et al. The healing effects of Centella extract and asiaticoside on acetic acid induced gastric ulcers in rats. Life Sci.2004,74(18):2237-2249.
[6]张选奋、郭树忠、张琳西等.TGF-β1对兔耳创面肉芽组织和瘢痕组织蛋白激酶C活性的影响.中国美容医学.2004,4(13)：140-142.
[7]曾维惠、王倩倩、覃静净、耿松梅、徐磊、聂建军等,ALA-PDT对兔耳增生性瘢痕抑制效应及作用机制的初步研究.中国美容医学2011,20(1):83-86
[8]王惠东,增生性瘢痕与瘢痕疙瘩致病相关基因的研究进展,中国美容医学.2008,17(7)：1098-1100
[9]李伟人、岑瑛、李晓红,病理性瘢痕中丙二醛、黄嘌呤氧化酶和总抗氧化能力的变化.中华整形外科杂志,2007,23(6):526-527
[10]李伟人、岑瑛、刘雪梅等,病理性瘢痕中主要氧化酶和抗氧化酶活性测定.生物学与生物物理进展,2007,34(8)：851-855
[11]刘忠、雷丽华、李旋、黄晓琴、程玉琪、易成刚等,米诺地尔对增生性瘢痕成纤维细胞及超氧化物岐化酶的影响.中国美容医学2009,18(6):826-828
[12]尚任初、夏照帆、杨珺等.成纤维细胞促进真皮替代物血管化的作用机制.中国修复重建外科杂志.2003,17(2)：100-103
[13]COOK H, DAVIES KJ. HARDING KG. et al. Defective extracellular matrix reorganization by chronicwound fibroblasts is assocjated with alterations in TIMP-1,TIMP-2. and MMP-2 activity. J Invest Dermatol,2000,115(2):225-233.
[14]Shi HP, Most D, Efron DT, et al. The role of inos in wound healing. Surgery.2001,130(2):225-229.
[15]Ring BD, Scully S, Davis CR, et al. Systemically and topically administered leptin both accelerate wound healing in diabetic ob/ob mice. Endocrinology.2000,14(1):446-449.
[16]Stallmeyer B, Kampfer H, Podda M, et al. A novel keratinocyte mitogen: regulation of leptin and its functional receptor in skin repair. J Invest Dermatol.2001,117(1):98-105.
[17]李培兵、金宏、刘佃辛等.瘦素促进大鼠皮肤创伤愈合作用的实验研究.中华医学杂志.2003,83(9)：800-802.
[18]Glasow A, Kiess W, Anderegg U, et al. Expression of leptin(ob) and leptin receptor (ob-R) in human fibroblasts:regulation of leptin secretion by insulin. J Clin Endocrinol Metab.2001,86(9):4472-4479.
[19]李培兵、金宏等.瘦素对体外大鼠成纤维细胞增值与胶原合成的影响.Chinese J Reparative and Reconstructive Surgery,2005. Vol 19(1).
[20]蔡紫光,彭旦明.增生陛瘢痕研究进展,实用中西医结合临床2010,10(3)：91-94
[21]赵文鲁、匡瑞霞、刘肃、陈璐等,积雪草甙对兔耳增生性瘢痕TGF-p mRNA表达的影响.中国美容医学2009,18(1):72-75
[22]Saulis AS. Mogford JH. Mustoe TA. Eflfect of M ederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002;110f11:177-183
[23]杨东运,李世荣,李钢,等.人皮肤移植增生性瘢痕裸鼠模型的建立,第三军医大学学报2004,26(10)：899
[24]李希军、柳大烈、王吉慧等.兔耳增生性瘢痕模型建立方法的探讨.中国美容医学.2006,5(15)：499-500.
[25]周勤生、马少林、董祥林等.兔耳增生性瘢痕模型的建立与应用.新疆医 科大报.2005,8(28)：746-748.
[26]李颖、王继华、何永静、杜永贵、刘垠、赵阳等,TNF-a抑制兔耳瘢痕增生的实验研究.中国美容医学2009,18(6):828-831
[27]曾海峰、韩晓霞、刘蓓、鲁开化、郭树忠等,他克莫司抑制兔耳瘢痕增生的作用及其机制研究.中国美容医学2011,20(1):68-70
[28]Tateshita T, Ono I, Kaneko F, et al. Effect of collagen matrix containing transforming growth factor (TGF)-beta (1) on wound contraction. Dermatol Sci 2001,27(2):104-113.
[29]王齐,聂芳菲,赵霞,等.Periostin在过度增生性瘢痕的表达及其与TGF-B1、和受体的相关性.中华整形外科杂志,2007,23(3)：229-232
[30]Fujiwara M, Muragaki Y, Oshima A. Dpregulation of transforminggrowth factor-betal and vascular endothelial growth factor in culturedkeloid fibroblasts:relevance to angiogenic activity. Arch DermatolRes,2005, 297:161-169
[31]王西樵,刘英开,毛志刚,等.增生性瘢痕中成纤维细胞生物学功能变化与微血管病理改变的研究。创伤外科杂志,2007,9(4)：311-314
[32]岳毅刚,蒋常文,李佩英,等.血管内皮生长因子抗体靶向血管治疗对增生性瘢痕工型胶原蛋白表达的影响.中华烧伤杂志,2006,22(6)：427-430
[1]Monica CT, Willem MV. Magda MW. et al. Prevention and curative management of hypertrophic scar formation. Bums,2009,35(4):463-475.
[2]王齐,聂芳菲,赵霞,等.Periostin在过度增生性瘢痕的表达及其与TGF-B1、和受体的相关性.中华整形外科杂志,2007,23(3)：229-232
[3]Fujiwara M, Muragaki Y, Oshima A. Upregulation of transforminggrowth factor-betal and vascular endothelial growth factor in culturedkeloid fibroblasts:relevance to angiogenic activity. Arch DermatolRes,2005, 297:161-169
[4]王西樵,刘英开,毛志刚,等.增生性瘢痕中成纤维细胞生物学功能变化与微血管病理改变的研究。创伤外科杂志,2007,9(4)：311-314
[5]岳毅刚,蒋常文,李佩英,等.血管内皮生长因子抗体靶向血管治疗对增生性瘢痕I型胶原蛋白表达的影响.中华烧伤杂志,2006,22(6):427-430
[6]高明月、蔺洁、张文显.增生性瘢痕的防治现状与展望.中国组织工程研究与临床康复.第14卷第20期2010,5(14):3753-3756
[7]余艳、王玮蓁,成纤维细胞与瘢痕的研究进展.湖北中志.2006,28(2)：55-56
[8]王惠东,增生性瘢痕与瘢痕疙瘩致病相关基因的研究进展,中国美容医学.2008,17(7)：1098-1100
[9]曹毅,郭建辉,陶茂灿,中药制剂对兔耳增生性瘢痕组织的影响.中华中医药学刊.2008,26(1)：96-97
[10]Chemof WG, Cramer H, Stephanie SH. The efficacy of topical silicone gel elastomers in the treatment of hypertrophic scars, keloid sears, and post-laser exfoliation erythema Aesthetic Plast Surg,2007, 31(5):495-500.
[11]Reno F, Sabbatini M, Lombardi F, et al. In vitro mechanical compression induces apoptosis and regulates cytokines release in hypertrophic sears. Wound Repair Regen,2003,11(5):331-336.
[12]Tayfim A, Kaan G, Mi that A. Combination of diferent techniques fortlle treatment of earlobe keloids. Aesth Plast Surg.2002,26:184-188
[13]Atiyeh BS. Nonsurgical management of hypertrophic scars:evidence-based therapies, standard practices, and emerging methods. Aesthetic Plast Surg,2007,31(5):468-492.
[14]Caccialanza M, Piccinno R, Schiem A. Postoperative radiotherapy of keloids:A twenty-year experience. Eur J Derm atol,2002,12:58-62
[15]张振、章一新.增生性瘢痕治疗的研究进展.组织工程与重建外科杂志.2010,6(3)：178-180
[16]Mustoe TA, Cooter RD, Gold MH, etal. International clinical recommendations on scar management. Plast Reconstr Surg,2002, 110(2):560-571.
[17]Bouzari N. Davis SC. Nouri K. Laser treatment of keloids and hypertrophic scars. Int J Dermatol,2007,46(1):80-88.
[18]Kuo YR, Wu WS, Jeng SF, et al. Activation of ERK and p38kinase mediated keloid fibmblast apoptosis after flashlamp pulsed-dye laser treatment. Lasers Surg Med,2005,36(1):31-37.
[19]李惠斌,蔡景龙.瘢痕疙瘩治疗研究进展.中华医学美学美容杂志,2004,10(2)：126
[20]李旋,刘达恩,欧增达等,丹参总酮对体外模拟人增生性瘢痕的作用.中华烧伤杂志,2009,25(1)：62-63
[21]万鲲,高申.旋复花提取物对人增生性瘢痕成纤维细胞抑制作用的研究.中国药物应用与监测,2007,4(6)：29-30,58
[22]赵文鲁、匡瑞霞、刘肃等,积雪草甙对兔耳增生性瘢痕TGF-β1mRNA表达的影响.中国美容医学,2009,18(1)：71-7
[23]蔡紫光,彭旦明.增生陛瘢痕研究进展,实用中西医结合临床2010,10(3)：91-94
[24]Saulis AS. Mogford JH. Mustoe TA. Eflfect of M ederma on hypertrophic scarring in the rabbit ear model. Plast Reconstr Surg 2002,110(1):177-183
[25]杨东运,李世荣,李钢,等.人皮肤移植增生性瘢痕裸鼠模型的建立,第 三军医大学学报2004,26(10)：899
[26]Lain QL, Lu L. Role of leptin in immunity. Cell Mol Immunol。 2007.4(1):1-13.
[27]Fietta P. Focus on leptin, a pleiotropic hormone. Minerva Med,2005, 96(2):65-75.
[28]Banks WA. The many lives of leptin. Peptidest 2004,25(3):331-338.
[29]Lin J. Yan GT。Hao XH. et. al. Effect of intestinal ischemia-reperfusion injury on protein levels of leptin and orexin-A inperipheral blood and central secretory tissues. World JGastroenterol,2005,11 (7):1000-1004.
[30]Niv-Spector L, Gonen-Berger D, Gourdou I, et al. Identificationof the hydrophobic strand in the A-B loop of leptin as majorbinding site 111: implicarions for large scale preparation of potentrecombinant human and ovine leptin antagonists. Bioehem J,2005,391 (Pt 2)：221-230.
[31]Zieba D. Amatalden M, Williams G. Regulatory roles of leptin inreproduction and metabolism:a comparative review. DomesticAnim Endoerinol,2005,29(1):166-185.
[32]WaelputWt Brouckae#tP, Broekaert. D, et al. A roleforleptininthe systemic inflammatory response syndrome(SIRS)and inimmune response, an 岬date. Curr Med Chem,2006.13(4)-.465-475.
[33]Marikovsky M, Rosenblum el。Faltin Z, et al. Appearance ofleptin in wound fluid " response to injury. Wound RepairRngen,2002,10(5):302-307.
[34]Murad A. Nath AK, Cha ST. et. al. Leptin is an autocrine/paracrine regulator of wound healing. FASEB J,2003t 17(13):1895-1897.
[35]李培兵.金宏.刘佃辛,等.瘦豪对体外大鼠成纤维细胞增殖与胶原台成的影响.中国修复重建外科杂志,2005,19(1):20-22.
[36]张凯、司艺玲、林季等瘦素及其抗体对小鼠皮肤创伤的修复作用标记免疫分析与临床1006-1703(2008)04-0231-03
[37]Glasow A, Kiess W, Anderegg U, et al. Expression of leptin(oB-Rb) in human fibroblasts:regulation of leptin secretion by insulin. J Clin Endocrinol Metab,2001,86(9):4472-4479.