术后伤口愈合——有助于减少术后炎症的大部分推荐产品是含抗氧化剂和抗炎剂的药妆品,包括各类皮肤屏障修复功能的保湿剂,可减少皮肤红肿和炎症。修复屏障完整性可以改善皮肤整体外观。通常建议屏障修复保湿剂的成分为表皮脂类,如神经酰胺、透明质酸（HA）（保湿剂）和锁水剂（用于非常干燥的肌肤）。非处方药妆品的某些成分可助于消除红肿和炎症，如维生素C、维生素E和维生素B或烟酰胺，将有助于维持皮肤屏障，还有抗炎的特性。此外，多酚类黄酮如大豆和绿茶，以及一些其他有机成分如咖啡因、野甘菊和甘草，可助于消炎。如果考虑术后外用维生素C，那么应使用非抗坏血酸衍生物。维生素C中抗坏血酸磷酸酯镁和抗坏血棕榈酸酯的pH为中性，耐受性更好。
除了目前的处方和非处方药妆品用于术后造成的刺激和炎症之外，还正在研究和尝试使用铜肽以及其它良好耐受性和有效的天然化合物。铜是一种杀菌剂，可以调控表皮中角化形成细胞整合素和细胞外基质重塑。细胞外基质包括结构性纤维胶原质，并由促进表皮形成的基质金属蛋白酶（MMPs）重塑或降解。MMPs的主要类别包括胶原酶（即MMP-1）和降解间质胶原和基底膜蛋白的明胶酶（即MMP-2和MMP-9）。MMPs的活性被内源性组织抑制剂金属蛋白酶（TIMPs）所抑制。铜是赖氨酰氧化酶的辅因子，交联胶原蛋白，并刺激成纤维细胞中，基质衍生三肽复合物（甘氨酰 - 组氨酰 - 赖氨酸或Gly-His-Lys[GHK]）中的MMP-2和胶原蛋白的表达。三肽如GHK和Gly- Gly-His，及其铜络合物，具有高活性和高皮肤耐受性。这些复合物已被证明在伤口愈合、组织修复和皮肤消炎的过程中发挥着生理作用。Gly-Gly-His、GHK，氯化铜及其铜络合物降低了成纤维细胞中肿瘤坏死因子α依赖性IL-6的分泌。IL-6对于正常的伤口愈合、皮肤发炎和UVB诱导型红斑至关重要。由于这些铜肽的抗炎特性，因此可能替代具有更多副作用的皮质类固醇或非类固醇抗炎药。
4肉毒神经毒素和其他类药妆品
注射填充剂
乙酰六肽-3：在寻找一种低毒性的肉毒神经毒素（BoNT）来治疗老化皮肤时，发现了肉毒神经毒素外用补剂——乙酰六肽-3（Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2）。它来自突触小体相关蛋白SNAP-25（分子量为25kDa）的N-末端，对突触小泡对接和融合至突触前膜,释放乙酰胆碱必不可少。它维持可溶性N-乙基马来酰亚胺 - 敏感因子结合蛋白受体（SNARE）复合物的形成和稳定，抑制囊泡对接和钙离子依赖性儿茶酚胺胞吐。此外，它可基本上抑制面部表达的肌肉反复收缩，与A型BoNT类似，但疗效略差。乙酰六肽-3可抑制30％的儿茶酚胺胞吐，并能够很好地渗入皮肤中。因此，BoNT的这种外用形式是一种有效的肌肉注射BoNT填充剂。
研究显示，乙酰六肽-3可以有效并安全地淡化皱纹，主要是眶周外侧部位。在一项早期的研究中，给予10名女性眶周一侧含10%六肽的乳剂，另一侧给予不含六肽的同一乳剂， 2次/日，持续30天。研究发现使用含六肽乳剂的一侧皱纹深度降低30%，而使用不含六肽乳剂的另一侧皱纹深度降低10%。没有观察到刺激性和毒性。在另一项试验中，给予10名女性眶周横纹处5%乙酰六肽-3面霜，2次/日，治疗30天后，皱纹深度淡化27%。一项双盲、安慰剂对比研究中，给予60名女性外用六肽以评估其疗效和安全性，研究发现使用含10%六肽乳剂的一侧祛皱效果达到48.9%，而安慰剂组疗效仅0%。结果类似于Blanes-Mira等人的研究，未发现副作用如刺激性或毒性。上述研究均采用硅树脂复制品分析测量皱纹深度。
外用乙酰六肽-3可有效减少皱纹，并且最好将之作为肌肉注射BoNT的辅助剂，因其肌注制通过直接注射入靶肌肉能够起到更好的效果；然而想要获得BoNT的效果，但又要避免注射疼痛的患者可以选择单独外用乙酰六肽-3。使用乙酰六肽-3作为肌肉注射BoNT补充治疗的患者，每次治疗无需多单元BoNT注射，某些部位也无需经常注射，从而注射次数和疼痛感会少些。上述实验中未见皮肤刺激的副作用。此外，其外用形式的急性毒性与A型BoNT（20 ng/kg）相比不显著（≥2000 mg/kg），测试中未观察到基因毒性，因此可成为肌肉注射的安全补充选项。
外用透明质酸：注射填充市的补剂——透明质酸（HA）。透明质酸（HA）是一种发现于皮肤细胞外基质的糖胺聚糖，对组织的水合作用显著。此外，其对细胞外基质分子的合成以及表皮细胞与环境的相互作用上至关重要。HA的锁水能力约为其体积的1000倍即每克HA结合6 L的水；然而，一旦人体成年后，HA的量减少至基线水平的5％，从而导致皮肤干燥，失去弹性并萎缩。虽然光老化皮肤由于硫酸软骨素蛋白多糖的增加，进而糖胺聚糖增加，但其反常地沉积于真皮浅层的弹性组织变性物质上，而不同于年轻皮肤观察到的弥漫性散布。
多种外用抗衰老产品中含有HA，但没有足够证据表明HA可以有效减少皱纹，且还存在其不能渗透入皮肤中的顾虑。这种担忧源于HA的原始分子直径为3000 nm，但细胞间隙仅为15-50nm这一事实，而透明膜的细胞间隙仅有6-10 nm。最近，日本科学家发现一种将HA分子直径减至5 nm（纳米HA）而又不改变其结构的方法。对33名女性一侧的眶周区域外用纳米HA，2次/日，持续8周，而另一侧不治疗，研究显示治疗一侧的水合作用改善，在第2、4和8周进行皮肤湿度测量时发现还在持续改善。2周后皮肤粗糙度减少，弹性增强，并在整个研究中一直持续。此外，使用色度仪发现第57天测量的红斑比第1天小。在Pavicic等人的早期研究中，评估了不同分子量——50、 130、300、800或2000 kDa的透明质酸（外用，0.1%）对眼周区域的祛皱疗效。对随机组76名女性一侧的眼周区域给予HA乳霜，另一侧给予安慰剂，2次/日，持续2月。，2月后与安慰剂相比，仅50-和130-kDa的HA制剂抗皱特性疗效显著。
外用HA不仅是祛皱的有效配方，更是那些不愿打针或刚出现皱纹的患者，正在寻求的一种无创治疗。此外，也给那些进行注射填充剂和BoNT疗法的患者带来了福音，因为外用药妆品和注射剂将同时靶向皱纹，只需更少单位的BoNT和/或填充剂以及注射次数，这意味着患者遭受更少的疼痛和副作用。
5结论
皮肤科医生需要为那些具有某些治疗禁忌症、不愿打针或没有大量术后恢复时间的美容患者，提供多种可替代的美容方案。了解这些方案并知道如何联合它们以改善疗效对于任何美容实践至关重要。
下附英文原文：
Postprocedure Wound Healing—Most of the recommended products that help decrease postprocedural inflammation are cosmeceuticals containing both antioxidants and anti-inflammatories to help decrease redness and inflammation, including various barrier repair moisturizers. Restoring barrier integrity improves the overall appearance of the skin. The ingredients normally recommended in barrier repair moisturizers are epidermal lipids such as ceramides; hyaluronic acid (HA), which is a humectant; and occlusives for patients with very dry skin.Some of the ingredients in over-the-counter cosmeceuticals that can help decrease redness and inflammation include vitamin C, vitamin E, and vitamin B or niacinamide, which will help plump the barrier and also have anti-inflammatory properties. Additionally, polyphenolic flavonoids such as soy and green tea can help decrease inflammation, along with a number of other organic ingredients, such as caffeine, feverfew, and licorice. If topical vitamin C is being considered for postprocedure use, the non–ascorbic acid variant should be administered. The magnesium ascorbyl phosphate and ascorbyl palmitate forms of vitamin C have a neutral pH and tend to be better tolerated by patients.
In addition to current prescription and overthe- counter cosmeceuticals used for postprocedure irritation and inflammation, copper peptides and other well-tolerated and effective naturally occurring compounds are being investigated and tried. Copper is a biocide that regulates keratinocyte integrins for epithelization and extracellular matrix remodeling. The extracellular matrix consists of the structural fibrillar collagens and is remodeled or degraded by matrix metalloproteinases (MMPs) that facilitate epithelization. The predominant classes of MMPs include collagenases (ie, MMP-1) and gelatinases (ie, MMP-2, MMP-9) that degrade interstitial collagen and basement membrane proteins. The MMPs are endogenously inhibited by tissue inhibitors of metalloproteinases (TIMPs). Copper is a cofactor to lysyl oxidase, which crosslinks collagen and stimulates expression of MMP-2 and collagen in a complex with a matrix-derived tripeptide (glycyl-histidyl-lysine or Gly-His-Lys [GHK]) in fibroblasts.Much attention has been focused on the tripeptides, such as GHK and Gly- Gly-His,and their copper complexes, which have high activity and good skin tolerance. These complexes have been shown to play a physiological role in the process of wound healing, tissue repair, and skin inflammation. Gly-Gly-His, GHK, copper chloride, and their copper complexes decrease tumor necrosis factor α–dependent IL-6 secretion in fibroblasts. IL-6 is crucial for normal wound healing, skin inflammation, and UVB-induced erythema.Because of their anti-inflammatory properties, these copper peptides could potentially be used in place of corticosteroids or nonsteroidal anti-inflammatory drugs, which have more side effects.
Botulinum Neurotoxin and Other
Injectable Fillers
Acetyl Hexapeptide-3: A Topical Complement to Botulinum Neurotoxin—Acetyl hexapeptide-3 (Ac-Glu-Glu-Met-Gln-Arg-Arg-NH2) was discovered when looking for a less toxic variation of botulinum neurotoxin (BoNT) to treat aging skin. It is patterned from the N-terminal end of the synaptosome-associated protein of molecular weight 25 kDa (SNAP-25), which is essential for docking and fusion of synaptic vesicles to the presynaptic membrane for acetylcholine release. It prevents formation and stability of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) complex, inhibiting vesicle docking and calcium-dependent catecholamine exocytosis. It also has been found to substantially inhibit the repetitive muscular contraction of facial expression similar to BoNT type A but with somewhat lower efficacy.Acetyl hexapeptide-3 was shown to inhibit 30% of total catecholamine exocytosis and had a remarkable capacity to permeate the skin.Thus this topical form of BoNT is a useful complement to intramuscular BoNT.
Studies showing the efficacy and safety of acetyl hexapeptide-3 have demonstrated reductions in wrinkle intensity, mainly in the lateral periorbital areas. In one early study, 10 women applied an emulsion containing 10% of the hexapeptide to one lateral periorbital region and the same emulsion without the hexapeptide to the contralateral side, both twice daily for 30 days. A 30% decrease in the depth of skin wrinkles was seen on the hexapeptide side compared with a 10% decrease in the depth of wrinkles on the side treated without hexapeptide. No irritation or toxicity was noted. In another trial, 10 women applied an acetyl hexapeptide-3 cream 5% twice daily to lateral periorbital rhytides, with a 27% improvement in wrinkle depth after a 30-day treatment period. A double-blind, placebo-controlled study of 60 women assessing the safety and efficacy of topical hexapeptide showed a total antiwrinkle efficacy of 48.9% on the side treated with an emulsion containing 10% of the hexapeptide compared with 0% efficacy on the placebo side. Similar to Blanes-Mira et al, no adverse events such as skin irritation or toxicity were seen. In all of these studies, wrinkle depth was measured by silicone replica analysis.
Topical acetyl hexapeptide-3 is effective in decreasing wrinkles, and its best use will likely be as an adjunct to intramuscular BoNT, as the intramuscular form likely has higher efficacy with the toxin injected directly into the target muscle; however, patients who want the effects of BoNT without the pain of injections may choose to use topical acetyl hexapeptide-3 alone. Patients who do use acetyl hexapeptide-3 as a complement to their intramuscular BoNT regimen may not need as many units of BoNT with each treatment or may not need certain areas injected as often, leading to fewer injections and less pain with each visit. Skin irritation was not seen as a side effect in these trials. Additionally, the topical form has insignificant acute toxicity (≥2000 mg/kg) compared to BoNT type A (20 ng/kg), and genotoxicity was not seen with testing, making it a safe complementary option to an injectable regimen.
Topical Hyaluronic Acid: A Complement to Injectable Fillers—Hyaluronic acid (HA) is a glycosaminoglycan found in the extracellular matrix of the skin that greatly contributes to tissue hydration.Additionally, it plays a crucial role in the synthesis of extracellular matrix molecules and epidermal cell interaction with the environment.The water-binding capacity of HA approximates 1000 times its volume or 6 L of water per gram of HA;however, once an individual reaches adulthood, the amount of HA decreases to 5% of baseline levels, thus contributing to xerosis, loss of skin elasticity, and atrophy. Although photoaged skin can have increased glycosaminoglycans due to an increase in chondroitin sulfate proteoglycans, they are abnormally deposited on elastotic material in the superficial dermis rather than diffusely scattered, as seen in youthful skin.
Many topical antiaging products contain HA, though evidence for efficacy in reducing wrinkles has been lacking, along with concerns that HA cannot penetrate the skin. This concern stems from the fact that the original molecule is 3000 nm in diameter and the intercellular space is only 15 to 50 nm. This space is only 6 to 10 nm at the hyaline membrane. Recently, scientists in Japan found a way to reduce the size of HA molecules to 5 nm (nano-HA) without changing its structure. A study of 33 women who applied the topical nano-HA twice daily for 8 weeks to one periorbital area while the contralateral side was left untreated showed improved hydration of the treated side that continued to increase when measured at 2, 4, and 8 weeks using corneometry. Roughness decreased and elasticity increased after week 2, which were maintained throughout the study. Additionally, erythema was measured using a chroma meter, which was found to have decreased at day 57 versus day 1. An earlier study by Pavicic et al evaluated the efficacy of topical hyaluronan 0.1% formulations of different molecular weights—50, 130, 300, 800, or 2000 kDa—in the periocular area. A randomized group of 76 women were treated twice daily for 2 months with HA cream on one side of the periocular area and placebo cream on the other. With regard to antiwrinkle properties, only the 50- and 130-kDa HA formulations showed marked effects compared with placebo after 2 months.
Topical HA would be an effective addition to an antiwrinkle regimen, especially in patients who are averse to needles or are just starting to get wrinkles and are looking for a noninvasive therapy. Additionally, it would be beneficial for patients who have an injectable filler and BoNT regimen, as these patients will be able to target wrinkles simultaneously with both topical cosmeceuticals and injectables and likely will need fewer units of BoNT and/or filler and possibly fewer injections over time, which translates to decreased pain and adverse outcomes for patients.
Conclusion
The myriad of options dermatologists have to offer patients for cosmetic enhancement provides alternatives for patients who have contraindications to certain treatments, are needle averse, or have lifestyles that do not afford them a great deal of postprocedural healing time. Being knowledgeable about these options and how to combine them for improved outcomes is essential to any cosmetic practice.
由MediCool医库软件李文婷 梁渝苓编译
原文来自：Cutis. ;94:122-126.
本文转载自：皮肤科周迅
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