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在大鼠模型中注射基于透明质酸的真皮填充剂后对皮肤细胞外基质的刺激

Skin extracellular matrix stimulation following injection of a hyaluronic acid-based dermal filler in a rat model.

作者信息

Paliwal Sumit, Fagien Steven, Sun Xiaojian, Holt Tyler, Kim Thomas, Hee Christopher K, Van Epps Dennis, Messina Darin J

机构信息

Goleta, Calif.; and Boca Raton, Fla. From Allergan, Inc., and Aesthetic Eyelid Plastic Surgery.

出版信息

Plast Reconstr Surg. 2014 Dec;134(6):1224-1233. doi: 10.1097/PRS.0000000000000753.

Abstract

BACKGROUND

Hyaluronic acid-based dermal fillers have gained rapid acceptance for treating facial wrinkles and deep tissue folds. Although their space-filling properties are well understood, this study evaluates the cellular and molecular changes in skin, as a secondary effect, following injection of a commercially available, 24-mg/ml, cross-linked hyaluronic acid-based filler (HYC-24L+) in a rodent model.

METHODS

Sprague-Dawley rats, aged 2 to 4 months, were injected intradermally with 20 μl of HYC-24L+ using a linear threading technique and followed to 12 weeks after injection. Untreated skin and saline injection were used as study controls. Enzyme-linked immunosorbent assay and reverse-transcriptase polymerase chain reaction methods were used to investigate changes in the expression of several extracellular matrix proteins and genes over time.

RESULTS

HYC-24L+ significantly increased the protein expression levels of collagen types I and III in rat dermal tissue for up to 12 weeks. The ratio of collagen type III to type I protein, however, remained unchanged, suggesting maintenance of collagen homeostasis. A significant increase in dermal elastin after HYC-24L+ injection was also observed. Gene expression analysis confirmed that several genes associated with extracellular matrix production and assembly were also transiently up-regulated, and that these changes temporally preceded those observed at the protein level.

CONCLUSION

In addition to its well-understood space-filling function, as a secondary effect, the authors demonstrate that HYC-24L+ stimulates the production of several extracellular matrix components, including dermal collagen and elastin.

摘要

背景

基于透明质酸的真皮填充剂已迅速被用于治疗面部皱纹和深层组织褶皱。尽管其填充特性已为人熟知,但本研究在啮齿动物模型中评估了注射市售的24毫克/毫升交联透明质酸填充剂(HYC - 24L +)后皮肤的细胞和分子变化,这是一种次要效应。

方法

使用线性穿针技术对2至4个月大的Sprague - Dawley大鼠进行皮内注射20微升HYC - 24L +,并在注射后随访至12周。未处理的皮肤和注射生理盐水作为研究对照。采用酶联免疫吸附测定法和逆转录聚合酶链反应方法研究几种细胞外基质蛋白和基因的表达随时间的变化。

结果

HYC - 24L +可使大鼠真皮组织中I型和III型胶原蛋白的蛋白表达水平显著提高,持续长达12周。然而,III型胶原蛋白与I型胶原蛋白的蛋白比例保持不变,表明胶原蛋白内稳态得以维持。注射HYC - 24L +后,真皮弹性蛋白也显著增加。基因表达分析证实,与细胞外基质产生和组装相关的几个基因也短暂上调,且这些变化在时间上先于在蛋白水平观察到的变化。

结论

除了其广为人知的填充功能外,作为次要效应,作者证明HYC - 24L +能刺激包括真皮胶原蛋白和弹性蛋白在内的几种细胞外基质成分的产生。

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