您好, 访客   登录/注册

PRP在瘢痕防治中的作用机制研究进展

来源:用户上传      作者:胡再昌 陈啸 侯团结 马乐 金俊俊 马坤 李平松

  [摘要]在创面愈合过程中总是伴随着瘢痕的产生,除了影响外观外,事实上有不少的瘢痕会有令人难受的瘙痒、疼痛及干裂,甚至产生瘢痕挛缩,影响五官或四肢关节的正常功能。目前,治疗瘢痕的方法主要包括手术、药物、激光等,但它们也有各自的局限性。PRP作为一种治疗瘢痕的新方法,已经在临床上取得了显著疗效,本文就目前PRP对瘢痕调节的作用机制进行综述。
  [关键词]富血小板血浆;瘢痕;生长因子;黑色素;透明质酸
  [中图分类号]R619+.6    [文献标志码]A    [文章编号]1008-6455(2019)12-0173-05
  Research Progress on the Mechanism of PRP in Scar Prevention and Treatment
  HU Zai-chang1,CHEN Xiao2, HOU Tuan-jie2, MA Le2 ,JIN Jun-jun1,MA Kun1,LI Ping-song2
  (1. Clinical Medical College Yangzhou University,Yangzhou 225000, Jiangsu,China; 2.Department of Burn and Plastic Surgery,Northern Jiangsu People’s Hospital,Yangzhou 225000,Jiangsu,China)
  Abstract: In the wound healing process, there is always a scar. In addition to the appearance, there are actually many scars that can cause uncomfortable itching, pain and chapped, and even scar contracture affects the normal function of the facial or limb joints. At present,the methods for treating scars mainly include surgery, drugs, lasers, etc. But they also have their own limitations. As a new method for treating scars, PRP has achieved positive clinical effects. This article reviews the current mechanism of PRP on the regulation of scar.
  Key words: platelet rich plasma; scars; growth factors; melanin; hyaluronic acid
  瘢痕是創面愈合的产物。各种组织受到较为严重的损伤均可能形成瘢痕,瘢痕是机体组织损伤修复的必然结果。在发达国家,每年有超过1亿人形成瘢痕,其中30%由于伤口愈合异常而变成增生性瘢痕或瘢痕疙瘩[1]。瘢痕患者不仅影响美观,还会给患者带来社会和心理障碍,有的影响机体功能还可能降低其生活质量。增生性瘢痕是人类独有的,它们一般不会出现在其他动物身上[2],它是一种纤维增生性疾病,其特征为凸起、红色、结节,无弹性,与正常瘢痕相比,经历缓慢和不完全消退[3]。
  1  PRP简介
  富血小板血浆(platelet rich plasma,PRP)是一种个性化的治疗方法,包括离心患者的血液并去除某些成分,以浓缩血小板的数量[4]。在大多数情况下,PRP被激活从血小板的膜内颗粒中释放生长因子,然后可用于各种治疗目的[4]。血小板活化发生在细胞内颗粒融合到血小板膜上,所含生长因子经过最后的修饰进入活跃状态并被释放[5]。在生理条件下,这些颗粒的含量在伤口愈合和止血中起中介作用。血小板同时含有α和致密颗粒,α颗粒储存生长因子,如:血小板源生长因子(PDGF)、转化生长因子β(TGF-β)和TGF-β家族的其他成员等,致密颗粒含有生物活性分子,如:血清素、组胺、腺苷等,可调节细胞膜通透性和局部炎症[6]。
  PRP疗法目前用于许多皮肤病学和非皮肤病学治疗,与其他治疗相结合,以增强总体结果[4]。PRP在治疗脱发、痤疮、创伤性瘢痕、收缩性瘢痕、皱纹、妊娠纹、慢性溃疡,以及增强激光表面重修和术后伤口愈合等均显示了积极的效果[7-9]。
  2  PRP的临床应用
  Carter等[10]发现将PRP应用在肢体的创面上,能够使创面形成排列有序的胶原纤维,减少瘢痕形成;加速创面上皮细胞更新进程,缩短创面愈合时间。Marx[11]在研究中认为,伤口的过度收缩可以形成瘢痕,特别是颌面部美学区形成瘢痕是非常不理想的愈合,在皮肤外科学中应用PRP可以使皮肤损害区产生快速及较少瘢痕的愈合。Cervelli [12]研究发现,PRP联合脂肪干细胞和激光治疗创伤性瘢痕,有明显改善作用;另一项研究也证明剥脱性激光联合PRP和自体脂肪移植物对萎缩性和收缩性瘢痕的治疗具有协同作用[13]。Asif等[14]比较了微针联合自体PRP与蒸馏水治疗萎缩性痤疮瘢痕的疗效,提出微针与PRP结合治疗萎缩性痤疮瘢痕更有效。对于痤疮瘢痕,有报道自体富血小板血浆结合铒激光治疗面部痤疮瘢痕具有明显疗效[15]。对于急性声带损伤,PRP通过诱导上皮生长因子受体(epithelial growth factor receptor, EGFR)分泌加速受损大鼠声带的上皮形成,并且PRP可以有助于防止瘢痕形成[16]。PRP对重睑成形术患者,结果显示有效,例如更短的恢复时间,减少的副作用和/或并发症,甚至改善了瘢痕的分辨率[17]。   3  PRP治疗的作用机制
  3.1 生长因子作用:在PRP中,这些生长因子的比例与体内正常比例相符,使生长因子之间有最佳的协同作用,这在一定程度上弥补了单一生长因子刺激创面修复不佳的缺点,应用PRP促进软组织损伤愈合,实际上就是体内正常愈合过程中的高度浓缩,使损伤的愈合过程大大加快,而又不会造成组织生长的失控。
  3.1.1 转化生长因子β(transfer growth factorβ,TGF-β):TGF-β在目前研究中,是与瘢痕形成关系最密切的细胞因子。TGF-β1在增生性瘢痕形成的发病机制中起重要作用[18]。增生性瘢痕成纤维细胞比正常皮肤成纤维细胞产生更多的TGF-β1蛋白和mRNA[18-19]。TGF-β1诱导成纤维细胞增殖和细胞外基质(ECM)成分的合成,包括弹性蛋白,纤维连接蛋白和胶原蛋白[20]。在体外,TGF-β1减少胶原酶介导的伤口基质降解,并通过诱导间接刺激基质生长PDGF。TGF-β1增强胶原凝胶的收缩,因此,也促进伤口收缩[21]。
  Seung[22]在其研究中,提出TGF-β1信号通路具有负反馈机制。Mori等先前报道过TGF-β负反馈机制的可能性。简而言之,当加入超过阈值量的TGF-β1时,激活TGF-β1负反馈机制。TGF-β1负反馈机制降低结缔组织生长因子(connective tissue growth factor,CTGF)基因转录和CTGF蛋白水平。Mori等[23]研究提示TGF-β可诱导皮肤纤维化,CTGF有助于维持纤维化状态。Colwell等[24]报道,增生性瘢痕中CTGF合成的阻断可能特异性地抵抗过多的胶原基质沉积,确保更多的生理膠原沉积模式占优势,从而减少瘢痕形成。CTGF基因转录和CTGF蛋白水平的降低可以改善增生性瘢痕。
  3.1.2 血小板衍化生长因子(platelet derived growth factor,PDGF):PDGF通过刺激成纤维细胞胶原合成以及其胶原酶活化,从而调节胞外基质的更新。在创面的角质形成细胞和成纤维细胞内有PDGF mRNA的表达,PDGF能够增加创面炎症细胞和成纤维细胞的浸润,以及肉芽组织和胶原的形成。但是,如果作用过度,则会导致瘢痕形成。Minoru等在体外研究表明,因瘢痕疙瘩中成纤维细胞表面PDGFα受体数量增加,导致瘢痕疙瘩中的成纤维细胞对PDGF敏感性增高。
  PDGF是在PRP凝胶中含量较高,其通过基质干细胞、成纤维细胞趋化作用集中于创面,激活巨噬细胞和成纤维细胞并产生大量转化生长因子-α(TGF-α)、表皮生长因子,缩短细胞分裂周期,促进成纤维细胞分化增殖、激发血管的再生来发挥促进伤口愈合的作用;PDGF还能够通过诱导成纤维细胞分泌TGF-β,加速合成与分泌纤维连接蛋白和胶原,在创面修复后改建局部组织减少瘢痕的产生[25]。
  3.1.3 表皮生长因子(epithelial growth factor,EGF):皮肤损伤后,局部使用PRP凝胶后可释放表皮生长因子,其不仅加速表皮生长,而且有增加结缔组织收缩和基质形成的作用。Kikuchi等[26]体外正常成纤维细胞及瘢痕疙瘩对照研究发现,TGF-β1、PDGF及γ-干扰素对上述两种成纤维细胞的作用无明显异常。Ryu YH等[27]研究表明,表皮生长因子(EGF)样重复和盘状I样结构域3(EDIL3)为一种治疗瘢痕疙瘩的潜在新治疗工具。然而,组胺和EGF可显著增加瘢痕疙瘩Ⅰ型胶原的形成,故表明组胺和EGF在瘢痕疙瘩的形成中可能具有某种作用,但目前尚无直接证据表明瘢痕与EGF形成有直接联系。
  3.1.4 成纤维细胞生长因子(fibroblast growth factor,FGF):目前研究发现[28],在培养的毛细血管内皮细胞中加入成纤维细胞生长因子,不仅可以诱导毛细血管样管腔形成、促进细胞增殖,而且可趋化血管内皮细胞迁移到胶原基质中。Edwards与Buckley等[29-30]发现,b FGF能刺激胶原酶的表达。Elaine等[31]发现,在肝素存在时,a FGF和b FGF在体外能够抑制正常成纤维细胞和病理性瘢痕的胶原合成。这是由于FGF对αⅠ型前胶原基因表达的下行调节作用所致。这一结果表明,FGF通过减少病理性瘢痕成纤维细胞胶原蛋白的过量沉积,从而防止病理性瘢痕的产生。
  3.1.5 肿瘤坏死因子α(tumor necrosis factor α,TNF-α):肿瘤坏死因子α对人皮肤成纤维细胞的增殖有显著的促进作用,并且促进聚胺多糖和Ⅰ、Ⅲ 型胶原的合成。TNF-α通过直接抑制纤维粘连蛋白的产生以及增加蛋白聚糖酶和成纤维细胞内胶原酶的活性,从而在皮肤纤维化过程中起着促进分解代谢的作用。Greenwel等[32]的研究显示,肿瘤坏死因子通过抑制CCAAT/增强剂结合蛋白抑制I型胶原的合成。因此,TNF-α在成纤维细胞中可能起着双重作用,既是诱导剂又是抑制剂。Feng C等[33]发现,在增生性瘢痕成纤维细胞中,TNF-α阳性细胞百分率明显低于正常皮肤细胞。这是由于成纤维细胞中TNF-α mRNA含量下降所致。在伤口愈合时,TNF-α的缺乏可能会导致胶原的过量沉积。
  3.1.6 骨形态发生蛋白(bone morphogenic proteins,BMPs):骨形态发生蛋白是TGF-β超家族的一个子集,是PRP中发现的一组生长因子[34-37]。BMP-4,BMP-7和较低程度的BMP-2,在正确的条件下都是干细胞的有效脂肪形成诱导剂,甚至是正常脂肪细胞分化所必需的[38-40]。最近的体外研究表明,某些骨形态发生蛋白(BMP)可诱导瘢痕成肌纤维细胞去分化和重组成脂肪细胞。由于血小板在其颗粒内含有BMP,因此富含血小板的血浆(PRP)可以充当将BMP递送至瘢痕形成或潜在瘢痕形成部位的载体。此外,当PRP与脂肪移植组织混合时,将协同的脂肪生长因子(包括BMP)释放,这有助于完成肌成纤维细胞的转化和脂肪形成。   在傷口愈合的小鼠模型中,证明在BMP影响下,活跃生长的毛囊诱导由肌成纤维细胞去分化成脂肪细胞引起的周围脂肪形成[41]。其他研究表明,BMPs,即BMP-4和7,通过拮抗TGF-β原肌成纤维细胞信号传导并诱导更大的PPARγ表达来阻止和逆转肌成纤维细胞分化[42-43]。这些发现支持BMP通过诱导瘢痕组织中肌成纤维细胞转化为脂肪组织来预防甚至减少瘢痕形成的可能作用。
  3.1.7 血管内皮生长因子(vascular endothelial growth factor ,VEGF):血管内皮生长因子,在体内体外都表现出特异性地促进血管内皮细胞的增殖并诱导血管生成作用,为细胞生长和新生血管网的建立提供营养。VEGF在瘢痕疙瘩和增生性瘢痕中的表达是近年研究的新课题。瘢痕疙瘩和增生性瘢痕的形成与角质形成细胞中VEGF过度表达有密切关系,其机制可能是VEGF通过旁分泌机制作用于血管内皮细胞,在真皮内诱导生成大量新生血管,并能通过某种机制调节成纤维细胞的活性[44],影响胶原的代谢,这与Detmar等[45]的观点一致。同时该组织的缺氧也可刺激细胞分泌VEGF[46]。
  3.2 抗炎作用:伤口感染是导致伤口愈后形成瘢痕和组织再生延迟的主要原因之一[47]。PRP经两次离心而获得,离心过程中,沉降系数相近的成分同时形成 ,所以离心形成的 PRP中含有大量的血小板及高浓度的白细胞。高浓度的白细胞能够起到促进伤口早期闭合及防止伤口感染的作用。最新研究证实[48],PRP中的巨噬细胞释放IL-1特定的原始抑制因子,控制早期炎症的发生。因此,PRP在创伤修复过程中能够明显降低炎症的发生[49]。
  研究表明[50],PRP对大肠杆菌、金黄色葡萄球菌(包括耐甲氧西林金黄色葡萄球菌、白色念珠菌和新型隐球菌)具有抗菌活性。有报道称[51],发现富含血小板的凝胶对甲氧西林敏感金黄色葡萄球菌(MSSA)有很强的抗菌作用,该活性与庆大霉素和西林类抗生素相当。痤疮丙酸杆菌常引起痤疮的发生,且痤疮好发于青春期男女面部,在痤疮愈后常会伴随瘢痕形成。有药敏实验显示[52],PRP对于痤疮丙酸杆菌有很强的抑制作用,同时其含有的大量生长因子可以促进创面愈合。另有研究指出[53],无论是否有白细胞,PRP制剂对大多数被检测的菌株均显示出抑菌特性。
  3.3 透明质酸:有研究报道[54],随着PRP浓度的增加,细胞合成的透明质酸与胶原的量有增加趋势。当PRP使用浓度接近50%时,其透明质酸与胶原的量增加幅度明显。由于缺少定量分析,PRP是通过使细胞数量增加,或是细胞合成量增加进而使透明质酸与胶原的量升高,还是两者共同作用,目前不得而知。胎儿无瘢痕愈合的主要特征是胎儿组织细胞外基质(extracellular matrix,ECM)成分与成年组织不同,成年人伤口的透明质酸和纤维蛋白仅短暂沉积,很快被胶原基质替代;胎儿无瘢痕愈合ECM成分与正常皮肤一致,透明质酸含量较高。
  透明质酸能将水分吸入透明质酸基质中,使其膨胀,从而产生体积和皮肤浮肿,并润滑组织。也有迹象表明[55],天然透明质酸促进细胞增殖和细胞外基质合成,调节胶原纤维直径。萎缩性瘢痕是炎症过程后胶原和弹性纤维丢失的常见并发症。因此笔者认为,PRP可以增加透明质酸与成纤维细胞胶原合成,用于重建丢失的胶原蛋白和弹性纤维,改善萎缩性瘢痕。
  3.4 黑色素:瘢痕的发生与皮肤黑色素成正相关,肤色越黑的人种,越容易发生病理性瘢痕。Burd等研究表明,TGF-β降低黑色素生成[56]。PRP中的TGF-β刺激基底膜蛋白的分泌,例如层粘连蛋白,IV型胶原和肌腱蛋白[57]。快速修复基底膜可能会减少色素沉着,如PRP联合二氧化碳点阵激光焕肤(fractional carbon dioxide resurfacing , FxCR)后色素沉着减少。PRP可以减少短暂色素沉着的确切机制仍有待考证,但它也有助于在接受FxCR皮肤再生的患者中获得最佳效果。
  4  展望
  富血小板血浆(PRP)是一种治疗瘢痕的新方法,也可作为微针射频、皮下注射、手术、皮肤微针等治疗的佐剂。自体PRP在作为佐剂时不仅减少了需要的治疗次数,而且降低了治疗的成本。然而,PRP激活和应用尚未标准化,导致多种不同的治疗方案具有不同的功效水平。PRP对于瘢痕的具体机制,尚未完全阐明,还有待进一步研究。
  [参考文献]
  [1]Mokos ZB,Anamaria J,Lovorka G,et al.Current therapeutic approach to hypertrophic scars[J]. Front Med,2017,4:83.
  [2]Mirastschijski U,Jokuszies A,Vogt PM.Skin wound healing: repair biology, wound, and scar treatment [J].Plast Surg,2012,3:267-296.
  [3]Wang R,Ghahary A,Shen Q,et al.Hypertrophic scar tissues and fibroblasts produce more transforming growth factor-beta1 mRNA and protein than normal skin and cells[J].Wound Repair Regen,2000,8(2):128-137.
  [4]Lynch MD,Bashir S.Applications of platelet-rich plasma in dermatology: A critical appraisal of the literature[J].Dermatolog Treat,2016,27(3):285-289.   [5]Dhurat R,Sukesh M.Principles and Methods of Preparation of Platelet-Rich Plasma: A Review and Author's Perspective[J].Cutan Aesthet Surg,2014,7(4):189-197.
  [6]Leo MS,Kumar AS,Kirit R,et al.Systematic review of the use of platelet-rich plasma in aesthetic dermatology[J].Cosmet Dermatol,2015,14(4):315-323.
  [7]Nofal E,Helmy A,Nofal A,et al.Platelet-rich plasma versus CROSS technique with 100% trichloroacetic acid versus combined skin needling and platelet rich plasma in the treatment of atrophic acne scars: a comparative study[J].Dermatol Surg,2014,40(8):864-873.
  [8]Nita AC,Orzan OA,Filipescu M,et al.Fat graft,laser CO2 and platelet-rich-plasma synergy in scars treatment[J].Med Life,2013,6(4):430-433.
  [9]Jones ME,McLane J,Adenegan R,et al.Advancing keloid treatment: a novel multimodal approach to ear keloids[J].Dermatol Surg,2017,43(9):1164-1169.
  [10]Carter CA,Jolly DG,Sr CEW,et al.Platelet-rich plasma gel promotes differentiation and regeneration during equine wound healing[J].Exp Mol Pathol,2003,74(3):244-255.
  [11]Marx R.Platelet-rich plasma:Growth factor enhancement for bone grafts[J].Oral Surg Oral Med Oral Pathol Oral Radiol Endod,1998,85(6):638-646.
  [12]Cervelli V,Nicoli F,Spallone D,et al.Treatment of traumatic scars using fat grafts mixed with platelet-rich plasma, and resurfacing of skin with the 1540 nm nonablative laser[J].Clin Exp Dermatol, 2012,37(1):55-61.
  [13]Nita A,Orzan O,Filipescu M,et al.Fat graft,laser CO2 and platelet-rich-plasma synergy in scars treatment[J].J Med Life,2013,6(4):430-433.
  [14]Asif M,Kanodia S,Singh K.Combined autologous platelet-rich plasma with microneedling versesmicroneedling with distilled water in the treatment of atrophic acne scars: a concurrent split-face study[J].Cosmet Dermatol,2016,15(4):434-443.
  [15]Zhu JT,Xuan M,Zhang YN,et al.The efficacy of autologous platelet-rich plasma combined with erbium fractional laser therapy for facial acne scars or acne[J].Mol Med Rep,2013,8(1):233-237.
  [16]Cobden SB,Oztrk K,Duman S,et al.Treatment of acute vocal fold injury with platelet-rich plasma [J].J Voice,2016,30(6):731-735.
  [17]Parra F,Morales DE,Campos R,et al.Effect of platelet-rich plasma on patients after blepharoplasty surgery[J].Orbit,2017,37(6):1-6.
  [18]Zhang Z,Garron TM,Li XJ,et al.Recombinant human decorin inhibits TGF-β-induced contraction of collagen lattice by hypertrophic scar fibroblasts[J].Burns,2009,35(4):527-537.   [19]Wang R,Ghahary A,Shen Q,et al.Hypertrophic scar tissues and fibroblasts produce more transforming growth factor mRNA and protein than normal skin and cells[J].Wound Repair  Regen,2001,8(2):128-137.
  [20]Rodland KD,Muldoon LL,Magun BE.Cellular mechanisms of TGF-beta action[J].J Invest Dermatol,1990,94(6 Suppl):33S.
  [21]Tateshita T,Ono I,Kaneko F.Effects of collagen matrix containing transforming growth factor (TGF)-β1 on wound contraction[J].J Dermatol Sci,2001,27(2):104-113.
  [22]Nam SM, Kim YB. The effects of platelet-rich plasma on hypertrophic scars fibroblasts[J].Int Wound J,2018,15(4):547-554.
  [23]Mori T,Kawara S,Shinozaki M,et al.Role and interaction of connective tissue growth factor with transforming growth factor-beta in persistent fibrosis: A mouse fibrosis model[J].Cell Physiol, 1999,181(1):153-159.
  [24]Colwell AS,Phan TT,Kong W,et al.Hypertrophic scar fibroblasts have increased connective tissue growth factor expression after transforming growth factor-beta stimulation[J].Plast Reconstr Surg 2005,116(5):1387-1390;discussion 1391-1392.
  [25]Eppley BL,Pietrzak WS,Blanton M. Platelet-rich plasma: a review of biology and applications in plastic surgery[J].Plast Reconstr Surg,2006,118(6):147e-159e.
  [26]Soma Y,Mizoguchi M,Yamane K,et al.Specific inhibition of human skin fibroblast chemotaxis to platelet-derived growth factor A-chain homodimer by transforming growth factor-β1[J].Arch Dermatol Res,2002,293(12):609-613.
  [27]Ryu YH,Lee YJ, Ki-Joo Kim,et al.Epidermal growth factor (EGF)-like repeats and discoidin I-Like domains 3 (edil3): a potential new therapeutic tool for the treatment of keloid scars[J].Tissue Engineering and Regenerative Medicine,2017,14(3):267-277.
  [28]Fukuda T, Kusuhara H, Nakagoshi T,et al.A basic fibroblast growth factor slow-release system combined to a biodegradable nerve conduit improves endothelial cell and Schwann cell proliferation: A preliminary study in a rat model[J].Microsurgery,2018,38(8):
   899-906.
  [29]Edwards AK,Heuvel MJ,Wessels JM,et al. Expression of angiogenic basic fibroblast growth factor, platelet derived growth factor, thrombospondin-1 and their receptors at the porcine maternal-fetal interface[J].Reprod Biol Endocrinol,2011,9(1):1-11.
  [30]Broadley KN,Aquino AM,Woodward SC,et al. Monospecific antibodies implicate basic fibroblast growth factor in normal wound repair[J].Lab Invest,1989,61(5):571-575.
  [31]Tan E M L,Rouda S,Greenbaum SS,et al.Acidic and basic fibroblast growth factors down-regulate collagen gene expression in keloid fibroblasts[J].Am J Pathol,1993,142(2):463-470.   [32]Greenwel P,Tanaka S,Penkov D,et al.Tumor necrosis factor alpha inhibits type I collagen synthesis through repressive CCAAT/enhancer-binding proteins[J].Mol Cell Biol,2000,20(3):912-918.
  [33]Feng C,Luo J.Experimental study of biologic effects of tumour necrosis factor-alpha on scar-derived fibroblasts[J].Zhonghua Zheng Xing Wai Ke Za Zhi,2000,16(1):27-29.
  [34]McElwee K,Hoffmann R.Growth factors in early hair follicle morphogenesis[J].Eur J Dermatol,2000,10(5):341-350.
  [35]Kang Q, Song WX, Luo Q,et al.A comprehensive analysis of the dual roles of BMPs in regulating adipogenic and osteogenic differentiation of mesenchymal progenitor cells[J].Stem Cells Dev,2009,18(4):545-559.
  [36]Cheng BH,Leng L,Wu MQ,et al.Expression analysis of bone morphogenetic protein 4 between fat and lean birds in adipose tissue and serum[J].Domest Anim Endocrinol,2016,56:13-19.
  [37]Yadav PS,Khan MP,Prashar P,et al.Characterization of BMP signaling dependent osteogenesis using a BMP depletable avianized bone marrow stromal cell line (TVA-BMSC)[J].Bone,2016,91:39-52.
  [38]Zhang Y,O'Keefe RJ,Jonason JH. BMP-TAK1 (MAP3K7) induces adipocyte differentiation through PPARgamma signaling[J].Cell Biochem,2017,118(1):204-210.
  [39]Sottile V,Seuwen K.Bone morphogenetic protein-2 stimulates adipogenic differentiation of mesenchymal precursor cells in synergy with BRL 49653 (rosiglitazone)[J].FEBS Lett,2000,475(3):201-204.
  [40]Huang H, Song TJ, Li X, et al BMP signaling pathway is required for commitment of C3H10T1/2 pluripotent stem cells to the adipocyte lineage[J].Proc Natl Acad Sci USA,2009,106(31):12670-12675.
  [41]Plikus MV,Guerrero-Juarez CF,Ito M,et al.Regeneration of fat cells from myofibroblasts during wound healing[J].Science,2017,355(6326):748-752.
  [42]Baraban E, Chavakis T, Hamilton BS, et al. Anti-inflammatory properties of bone morphogenetic protein 4 in human adipocytes[J].Int J Obes,2016,40(2):319-327.
  [43]Midgley AC,Duggal L,Jenkins R,et al.Hyaluronan regulates bone morphogenetic protein-7-dependent prevention and reversal of myofibroblast phenotype[J].J Biol Chem,2015,290(18):11218-11234.
  [44]Altavilla D,Saitta A,Cucinotta D,et al.Inhibition of lipid peroxidation restores impaired vascular endothelial growth factor expression and stimulates wound healing and angiogenesis in the genetically diabetic mouse[J].Diabetes,2001,50(3):667-674.
  [45]Detmar, Michael.The role of VEGF and thrombospondins in skin angiogenesis[J].J Dermatol Sci,2000,24(Supplement 1):S78-S84.   [46]Funayama E,Chodon T,Oyama A,et al.Keratinocytes promote proliferation and inhibit apoptosis of the underlying fibroblasts: an important role in the pathogenesis of keloid[J].J Invest Dermatol,2003,121(6):1326-1331.
  [47]Evanson JR,Guyton MK,Oliver DL,et al.Gender and age differences in growth factor concentrations from platelet-rich plasma in adults[J].Mil Med,2014,179(7):799-805.
  [48]Woodall JJr,Tucci M,Mishra A,et al.Celluar effects of platelet rich plasmainterleukin1 release from prp treated macrophsges[J].Biomed Sci Instrum,2008,44(7):489-494.
  [49]Marx RE.Platelet-rich Plasma (prp): What is prp and what is not prp?[J].Implant Dent,2001, 10(4):225-228.
  [50]Burnouf T ,Ming-Li Chou,Yu-Wen Wu, et al.Antimicrobial activity of platelet (PLT)-poor plasma, PLT-rich plasma,PLT gel,and solvent/detergent-treated PLT lysate biomaterials against wound bacteria[J].Transfusion,2013,53(1):138-146.
  [51]Jones RN, Nccls.Performance Standards for Antimicrobial Disk Susceptibility Tests[J]. Antimicrobic Newsletter,1984,1(8):64-65.
  [52]Schmitz JP,Hollinger JO.The biology of platelet-rich plasma[J].J Oral Maxillofac Surg,2001,59(9):1119-1121.
  [53]Federica D’asta,Halstead F,Harrison P,et al.The contribution of leucocytes to the antimicrobial activity of platelet-rich plasma preparations: a systematic review[J].Platelets,2018,29(1):9-20.
  [54]Gilbertie JM,Long JM,Schubert AG,et al.Pooled platelet-rich plasma lysate therapy increases synoviocyte proliferation and hyaluronic acid production while protecting chondrocytes from synoviocyte-derived inflammatory mediators[J].Front Vet Sci,2018,5:150-159.
  [55]Shin MK,Lee JH,Lee SJ,et al.Platelet-rich plasma combined with fractional laser therapy for skin rejuvenation[J].Dermatol Surg,2012,38(4):623-630.
  [56]Burd A,Zhu N,Poon VKM.A study of Q-switched Nd:YAG laser irradiation and paracrine function in human skin cells[J].Photodermatol Photoimmunol Photomed,2010,21(3):131-137.
  [57]Tamariz-Dominguez E,Castro-Munozledo F,Kuri-Harcuch W.Growth factors and extracellular matrix proteins during wound healing promoted with frozen cultured sheets of human epidermal keratinocytes[J]. Cell Tissue Res,2002,307(1):79-89.
  [收稿日期]2019-04-14
  本文引用格式:胡再昌,陳啸,侯团结,等.PRP在瘢痕防治中的作用机制研究进展[J].中国美容医学,2019,28(12):173-177.
转载注明来源:https://www.xzbu.com/6/view-15075807.htm