增生性瘢痕治疗研究进展
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摘要
增生性瘢痕是创面修复过程中细胞外基质过度沉积的产物,具体的分子生物学水平发病机制尚不明确,临床治疗也缺乏可靠的标准。为此,笔者于本研究中将增生性瘢痕的治疗现状,尤其是注射中药制剂、基因调控和激光在增生性瘢痕治疗中所取得的研究成果进行了综述,旨在为增生性瘢痕治疗的进一步研究提供线索与思路。
Hypertrophic scar is the product of excessive deposition of extracellular matrix during wound repair, of which the pathogenesis at the molecular biological level remains unclear and no reliable treatment standard is available in clinical practice. Therefore, this study reviewed the current treatment status of hypertrophic scars, especially the achievements of TCM preparation injection, gene regulation and laser in the treatment of hypertrophic scar, with the aim of providing some clues and thoughts for its further research.
Hypertrophic scar is the product of excessive deposition of extracellular matrix during wound repair, of which the pathogenesis at the molecular biological level remains unclear and no reliable treatment standard is available in clinical practice. Therefore, this study reviewed the current treatment status of hypertrophic scars, especially the achievements of TCM preparation injection, gene regulation and laser in the treatment of hypertrophic scar, with the aim of providing some clues and thoughts for its further research.
引文
[1] Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars:pathophysiology, classification, and treatment[J]. Dermatol Surg, 2017, 43(1):S3-S18.
[2]刘英开,王西樵,宋菲,等.增生性瘢痕中胶原结节的组织学特征[J].中华创伤杂志,2014, 30(4):302-306.
[3]宋菲,刘英开,王西樵.增生性瘢痕发生和演变过程中微血管和氧分压动态变化的研究[J].上海交通大学学报(医学版),2016, 36(11):1553-1557.
[4] Hellstrm M, Hellstr()m S, Engstr()m-Laurent A, et al. The structure of the basement membrane zone differs between keloids, hypertrophic scars and normal skin:a possible background to an impaired function[J]. J Plast Reconstr Aesthet Surg, 2014, 67(11):1564-1572.
[5]胥广,黄东.增生性瘢痕形成机制及治疗的现况与展望[J].现代医院,2015, 15(2):10-14.
[6]孙桂芳,张晓芬,陈亚峰,等.转化生长因子-β1/Smads信号在增生性瘢痕形成中的作用研究进展[J].创伤外科杂志,2015, 17(5):473-477.
[7]黄克华,周国富,陈朗.转化生长因子-β1与表皮生长因子在成人增生性瘢痕中的表达及意义[J].川北医学院学报,2016, 31(4):548-552.
[8]张羽飞,李厚忠,王学勇,等.增生性瘢痕形态学观察及血管内皮生长因子和转化生长因子β激活性激酶1表达的检测与意义[J].中国医学科学院学报,2015, 37(4):446-450.
[9] Zimna A, Kurpisz M. Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis:applications and therapies[J]. BioMed Res Int, 2015(4):1-13.
[10]王西樵,宋菲,陈雪莲,等.增生性瘢痕发生和演变过程中微血管通透性变化的研究[J/CD].中华损伤与修复杂志:电子版,2013, 8(1):20-22.
[11]任海涛,李媛,王盛东,等.内皮抑素预处理对人皮肤成纤维细胞纤维化的作用和机制[J].中华烧伤杂志,2017, 33(11):694-698.
[12]潘厚儒,陈曦,张润田,等.活血除痹汤对硬皮病小鼠皮肤血小板衍生生长因子A和转移生长因子-β表达的影响[J].中国中医药信息杂志,2017, 24(3):48-52.
[13]聂玉红,瞿雯,邢怡桥,等.PDGF对人RPE细胞中MMP-2、MMP-9和TIMP-1表达的影响[J].中华实验眼科杂志,2014, 32(1):6-11.
[14] Seifert 0, Bayat A, Geffers R, et al. Identification of unique gene expression patterns within different lesional sites of keloids[J]. Wound Repair Regen, 2008, 16(2):254-265.
[15]胡洋红,胡杨柳,刘德伍,等.增生性瘢痕与正常皮肤组织差异表达基因的筛选与生物信息学分析[J].南方医科大学学报,2014, 34(7):939-944.
[16] Liechty KW, Adzick NS, Crombleholme TM. Diminished interleukin 6(IL-6)production during scarless human fetal wound repair[J]. Cylokine, 2000, 12(6):671-676.
[17] van den Broek LJ, van der Veer WM, de Jong EH, et al. Suppressed inflammatory gene expression during human hypertrophic scar compared to normolrophic scar formation[J]. Exp Dermatol,2015, 24(8):623-629.
[18]詹建珍,陈琼芳.丹参酮ⅡA诱导瘢痕疙瘩成纤维细胞凋亡及周期阻滞研究[J].按摩与康复医学,2015, 6(3):78-79.
[19]刘华,杨华莲,周淑芳,等.丹参酮ⅡA磺酸钠对瘢痕成纤维细胞增殖及转化生长因子β1和α平滑肌肌动蛋白mRNA及蛋白表达的影响[J].中华烧伤杂志,2013, 29(3):294-299.
[20]康春福,陈斌,秦泽莲,等.丹参酮ⅡA磺酸钠在低氧下对瘢痕疙瘩成纤维细胞增殖和促纤维化因子表达的影响[J].中国微创外科杂志,2015,15(7):649-654.
[21]范雪梅,任桂香,梁琼麟,等.丹参脂溶性成分抑制体外血管新生及机制研究[J].中国中药杂志,2014, 39(4):744-747.
[22]刘嘉楠,何放,钱明元,等.丹参酮ⅡA磺酸钠对烧伤植皮创面愈合及瘢痕形成的影响[J].现代生物医学进展,2016, 16(7):1306-1308.
[23]付昱,张良,杨静,等.黄芪总苷液对瘢痕疙瘩成纤维细胞生长作用研究[J].中国药师,2016,19(9):1644-1647.
[24]张艳.黄芪对增生性瘢痕TGF-β1的表达及其Smad3信号途径的影响[D].重庆:重庆医科大学,2010.
[25] Chen X,Peng LH, Shan YH, et al. Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery[J]. Int J Pharm, 2013, 447(1-2):171-181.
[26]胡营杰.黄芪、水蛭有效组分对大鼠系膜细胞NF-κB、IκB、PDGF-BB、MMP-9的影响[D].南京:南京中医药大学,2016.
[27]地里夏提·库尔班.微小RNA21和TGF-β1在正常皮肤和增生性瘢痕组织中的表达研究[J].中国美容医学,2017, 26(10):68-70.
[28]赵亚亚,钟成,李悦,等.TGF-β1介导的Smad通路在肾脏纤维化中的作用及机制[J].解放军预防医学杂志,2018,36(4):427-430, 458.
[29] Loiselle AE, Yukata K, Geary MB, et al. Development of antisense oligonucleotide(ASO)technology against Tgf-βsignaling to prevent scarring during flexor tendon repair[J]. J Orthop Res,2015, 33(6):859-866.
[30] Zhou R, Zhang Q, Zhang Y, et al. Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars[J]. Exp Cell Res, 2015, 339(2):360-366.
[31] Li Q, Zhang DX, Wang YB, et al. MiR-21/Smad7 signaling determines TGF-β1-induced CAF formation[J]. Sci Rep, 2013(3):2038.
[32]张奇,王琛. microRNA-21调控TGF-β通路促进增生性瘢痕形成的机制研究[J].组织工程与重建外科杂志,2014,10(6):318-323.
[33]张羽飞,李厚忠,王学勇,等.增生性瘢痕形态学观察及血管内皮生长因子和转化生长因子β激活性激酶1表达的检测与意义[J].中国医学科学院学报,2015, 37(4):446-450.
[34]陈煜华,鲁开化,刁建升,等.靶向沉默血管内皮生长因子对兔耳增生性瘢痕的影响[J].中国美容整形外科杂志,2013, 24(3):144-147.
[35]丁金萍,陈博,曹谊林.病理性瘢痕激光治疗的研究进展[J].组织工程与重建外科杂志,2016, 12(2):141-143.
[36] Manuskiatti W,Iamphonrat T, Wanitphakdeedecha R, et al.Comparison of fractional erbium-doped yttrium aluminum garnet and carbon dioxide lasers in resurfacing of atrophic acne scars in Asians[J]. Dermatol Surg, 2013, 39(1 Pt1):111-120.
[37]张幸存,李大铁,安丽莎,等.IPL与595 nmPDL对兔耳增生性瘢痕PCNA及TGF-β1蛋白表达的影响[J].中国皮肤性病学杂志,2014, 28(2):123-127.
[38] Brewin MP, Lister TS. Prevention or treatment of hypertrophic burn scarring:a review of when and how to treat with the pulsed dye laser[J]. Bums, 2014, 40(5):797-804.
[39]李洁,濮哲铭,章一新.PDL和长脉宽Nd:YAG在早期瘢痕治疗中的疗效对比[J].组织工程与重建外科杂志,2018,14(2):73-75, 86.
[40] Koike S, Akaishi S, Nagashima Y, et al. Nd:YAG laser treatment for keloids and hypertrophic scars:an analysis of 102 cases[J]. Plast Reconstr Surg Glob Open, 2015, 2(12):e272.
[41] Giordano CN, Ozog D. Microstructural and molecular considerations in the treatment of scars with ablative fractional lasers[J].Semin Cutan Med Surg, 2015, 34(1):7-12.
[42]孙雯佳,吴家强,项蕾红.点阵射频在皮肤美容领域的应用[J].中华皮肤科杂志,2016, 49(10):751-754.
[43] Mignon C, Rodriguez AH, Palero JA, et al. Fractional laser photothermolysis using Bessel beams[J]. Biomed Opt Express,2016, 7(12):4974-4981.
[44]刘秀峰,潘文东,张元文,等.增生性瘢痕的激光治疗进展[J].中国美容医学,2015, 24(18):78-81.
[45] Choi JE, Oh GN, Kim JY, et al. Ablative fractional laser treatment for hypertrophic scars:comparison between Er:YAG and C02 fractional lasers[J].J Dermatolog Treat, 2014, 25(4):299-303.
[46] Seifert 0, Mrowietz U. Keloid scarring:bench and bedside[J]. Arch Dermatol Res, 2009, 301(4):259-272.
[47] Marneros AG, Norris JE, Watanabe S, et al. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23and 7p11[J]. J Invest Dennatol, 2004, 122(5):1126-1132.
[2]刘英开,王西樵,宋菲,等.增生性瘢痕中胶原结节的组织学特征[J].中华创伤杂志,2014, 30(4):302-306.
[3]宋菲,刘英开,王西樵.增生性瘢痕发生和演变过程中微血管和氧分压动态变化的研究[J].上海交通大学学报(医学版),2016, 36(11):1553-1557.
[4] Hellstrm M, Hellstr()m S, Engstr()m-Laurent A, et al. The structure of the basement membrane zone differs between keloids, hypertrophic scars and normal skin:a possible background to an impaired function[J]. J Plast Reconstr Aesthet Surg, 2014, 67(11):1564-1572.
[5]胥广,黄东.增生性瘢痕形成机制及治疗的现况与展望[J].现代医院,2015, 15(2):10-14.
[6]孙桂芳,张晓芬,陈亚峰,等.转化生长因子-β1/Smads信号在增生性瘢痕形成中的作用研究进展[J].创伤外科杂志,2015, 17(5):473-477.
[7]黄克华,周国富,陈朗.转化生长因子-β1与表皮生长因子在成人增生性瘢痕中的表达及意义[J].川北医学院学报,2016, 31(4):548-552.
[8]张羽飞,李厚忠,王学勇,等.增生性瘢痕形态学观察及血管内皮生长因子和转化生长因子β激活性激酶1表达的检测与意义[J].中国医学科学院学报,2015, 37(4):446-450.
[9] Zimna A, Kurpisz M. Hypoxia-inducible factor-1 in physiological and pathophysiological angiogenesis:applications and therapies[J]. BioMed Res Int, 2015(4):1-13.
[10]王西樵,宋菲,陈雪莲,等.增生性瘢痕发生和演变过程中微血管通透性变化的研究[J/CD].中华损伤与修复杂志:电子版,2013, 8(1):20-22.
[11]任海涛,李媛,王盛东,等.内皮抑素预处理对人皮肤成纤维细胞纤维化的作用和机制[J].中华烧伤杂志,2017, 33(11):694-698.
[12]潘厚儒,陈曦,张润田,等.活血除痹汤对硬皮病小鼠皮肤血小板衍生生长因子A和转移生长因子-β表达的影响[J].中国中医药信息杂志,2017, 24(3):48-52.
[13]聂玉红,瞿雯,邢怡桥,等.PDGF对人RPE细胞中MMP-2、MMP-9和TIMP-1表达的影响[J].中华实验眼科杂志,2014, 32(1):6-11.
[14] Seifert 0, Bayat A, Geffers R, et al. Identification of unique gene expression patterns within different lesional sites of keloids[J]. Wound Repair Regen, 2008, 16(2):254-265.
[15]胡洋红,胡杨柳,刘德伍,等.增生性瘢痕与正常皮肤组织差异表达基因的筛选与生物信息学分析[J].南方医科大学学报,2014, 34(7):939-944.
[16] Liechty KW, Adzick NS, Crombleholme TM. Diminished interleukin 6(IL-6)production during scarless human fetal wound repair[J]. Cylokine, 2000, 12(6):671-676.
[17] van den Broek LJ, van der Veer WM, de Jong EH, et al. Suppressed inflammatory gene expression during human hypertrophic scar compared to normolrophic scar formation[J]. Exp Dermatol,2015, 24(8):623-629.
[18]詹建珍,陈琼芳.丹参酮ⅡA诱导瘢痕疙瘩成纤维细胞凋亡及周期阻滞研究[J].按摩与康复医学,2015, 6(3):78-79.
[19]刘华,杨华莲,周淑芳,等.丹参酮ⅡA磺酸钠对瘢痕成纤维细胞增殖及转化生长因子β1和α平滑肌肌动蛋白mRNA及蛋白表达的影响[J].中华烧伤杂志,2013, 29(3):294-299.
[20]康春福,陈斌,秦泽莲,等.丹参酮ⅡA磺酸钠在低氧下对瘢痕疙瘩成纤维细胞增殖和促纤维化因子表达的影响[J].中国微创外科杂志,2015,15(7):649-654.
[21]范雪梅,任桂香,梁琼麟,等.丹参脂溶性成分抑制体外血管新生及机制研究[J].中国中药杂志,2014, 39(4):744-747.
[22]刘嘉楠,何放,钱明元,等.丹参酮ⅡA磺酸钠对烧伤植皮创面愈合及瘢痕形成的影响[J].现代生物医学进展,2016, 16(7):1306-1308.
[23]付昱,张良,杨静,等.黄芪总苷液对瘢痕疙瘩成纤维细胞生长作用研究[J].中国药师,2016,19(9):1644-1647.
[24]张艳.黄芪对增生性瘢痕TGF-β1的表达及其Smad3信号途径的影响[D].重庆:重庆医科大学,2010.
[25] Chen X,Peng LH, Shan YH, et al. Astragaloside IV-loaded nanoparticle-enriched hydrogel induces wound healing and anti-scar activity through topical delivery[J]. Int J Pharm, 2013, 447(1-2):171-181.
[26]胡营杰.黄芪、水蛭有效组分对大鼠系膜细胞NF-κB、IκB、PDGF-BB、MMP-9的影响[D].南京:南京中医药大学,2016.
[27]地里夏提·库尔班.微小RNA21和TGF-β1在正常皮肤和增生性瘢痕组织中的表达研究[J].中国美容医学,2017, 26(10):68-70.
[28]赵亚亚,钟成,李悦,等.TGF-β1介导的Smad通路在肾脏纤维化中的作用及机制[J].解放军预防医学杂志,2018,36(4):427-430, 458.
[29] Loiselle AE, Yukata K, Geary MB, et al. Development of antisense oligonucleotide(ASO)technology against Tgf-βsignaling to prevent scarring during flexor tendon repair[J]. J Orthop Res,2015, 33(6):859-866.
[30] Zhou R, Zhang Q, Zhang Y, et al. Aberrant miR-21 and miR-200b expression and its pro-fibrotic potential in hypertrophic scars[J]. Exp Cell Res, 2015, 339(2):360-366.
[31] Li Q, Zhang DX, Wang YB, et al. MiR-21/Smad7 signaling determines TGF-β1-induced CAF formation[J]. Sci Rep, 2013(3):2038.
[32]张奇,王琛. microRNA-21调控TGF-β通路促进增生性瘢痕形成的机制研究[J].组织工程与重建外科杂志,2014,10(6):318-323.
[33]张羽飞,李厚忠,王学勇,等.增生性瘢痕形态学观察及血管内皮生长因子和转化生长因子β激活性激酶1表达的检测与意义[J].中国医学科学院学报,2015, 37(4):446-450.
[34]陈煜华,鲁开化,刁建升,等.靶向沉默血管内皮生长因子对兔耳增生性瘢痕的影响[J].中国美容整形外科杂志,2013, 24(3):144-147.
[35]丁金萍,陈博,曹谊林.病理性瘢痕激光治疗的研究进展[J].组织工程与重建外科杂志,2016, 12(2):141-143.
[36] Manuskiatti W,Iamphonrat T, Wanitphakdeedecha R, et al.Comparison of fractional erbium-doped yttrium aluminum garnet and carbon dioxide lasers in resurfacing of atrophic acne scars in Asians[J]. Dermatol Surg, 2013, 39(1 Pt1):111-120.
[37]张幸存,李大铁,安丽莎,等.IPL与595 nmPDL对兔耳增生性瘢痕PCNA及TGF-β1蛋白表达的影响[J].中国皮肤性病学杂志,2014, 28(2):123-127.
[38] Brewin MP, Lister TS. Prevention or treatment of hypertrophic burn scarring:a review of when and how to treat with the pulsed dye laser[J]. Bums, 2014, 40(5):797-804.
[39]李洁,濮哲铭,章一新.PDL和长脉宽Nd:YAG在早期瘢痕治疗中的疗效对比[J].组织工程与重建外科杂志,2018,14(2):73-75, 86.
[40] Koike S, Akaishi S, Nagashima Y, et al. Nd:YAG laser treatment for keloids and hypertrophic scars:an analysis of 102 cases[J]. Plast Reconstr Surg Glob Open, 2015, 2(12):e272.
[41] Giordano CN, Ozog D. Microstructural and molecular considerations in the treatment of scars with ablative fractional lasers[J].Semin Cutan Med Surg, 2015, 34(1):7-12.
[42]孙雯佳,吴家强,项蕾红.点阵射频在皮肤美容领域的应用[J].中华皮肤科杂志,2016, 49(10):751-754.
[43] Mignon C, Rodriguez AH, Palero JA, et al. Fractional laser photothermolysis using Bessel beams[J]. Biomed Opt Express,2016, 7(12):4974-4981.
[44]刘秀峰,潘文东,张元文,等.增生性瘢痕的激光治疗进展[J].中国美容医学,2015, 24(18):78-81.
[45] Choi JE, Oh GN, Kim JY, et al. Ablative fractional laser treatment for hypertrophic scars:comparison between Er:YAG and C02 fractional lasers[J].J Dermatolog Treat, 2014, 25(4):299-303.
[46] Seifert 0, Mrowietz U. Keloid scarring:bench and bedside[J]. Arch Dermatol Res, 2009, 301(4):259-272.
[47] Marneros AG, Norris JE, Watanabe S, et al. Genome scans provide evidence for keloid susceptibility loci on chromosomes 2q23and 7p11[J]. J Invest Dennatol, 2004, 122(5):1126-1132.