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纳米粒型多烯磷脂酰胆碱对脂肪组织的脂肪分解作用:首次有前景的体外和体内研究结果。

Lipolytic effects of nano particle sized polyenylphosphatidylcholine on adipose tissue: First promising in vitro and in vivo results.

机构信息

Center of Plastic-, Hand- and Reconstructive Surgery, University Hospital Regensburg, Regensburg, Germany.

Department of Orthopaedics, University Children's Hospital, Basel, Switzerland.

出版信息

Clin Hemorheol Microcirc. 2020;75(2):189-199. doi: 10.3233/CH-190715.

Abstract

BACKGROUND

Lipolytic injectables for body contouring procedures have been reported for necrotic effects on adipose tissue causing side effects as swelling, pain and hematoma. Deoxycholic acid is widely used as a solvent in lipolytic injectables and is associated with necrosis when applied to cells. A new lipolytic preparation (NWL-10) containing only polyenylphosphatidylcholine in nano particle size, glycerrhizinate and maltose has been reported for its lipolytic action on adipose tissue. However, no data exist whether the NWL-10 mixture is responsible for apoptosis or necrosis in adipose tissue which can be associated with severer side effects as reported for deoxycholic acid preparation.

METHODS

3T3-L1 mouse cells and human adipose tissue derived stem cells were exposed to the NWL-10 mixture and to each ingredient of the mix in order to investigate cytotoxic, lipolytic, necrotic or apoptotic effects. Furthermore, a Balb/C mouse animal model was used to investigate inflammatory responses to NWL-10 by bioluminescence monitoring and histological examination.

RESULTS

A high extent of lipolysis was detected for the NWL-10 mixture when applied to both cell types with no cytotoxic effect. Interestingly, low concentration of NWL-10 resulted in necrosis whereas high concentration of NWL-10 showed a certain amount of apoptosis. Application of single ingredients of NWL-10 or various combinations of two component mixtures did not result in any apoptosis or necrosis. In addition, no inflammatory effects of NWL-10 were observed in the mouse model.

CONCLUSIONS

The NWL-10 mixture provided promising results regarding lipolysis on adipose tissue with limited apoptosis and necrosis when compared to currently available injectables. These first promising results require further fundamental and more detailed research on essentials for drug approval. NWL-10 has the potential to become a second generation product for future lipolytic injectables.

摘要

背景

用于身体轮廓塑形手术的脂肪分解注射剂已被报道对脂肪组织有坏死作用,导致肿胀、疼痛和血肿等副作用。脱氧胆酸广泛用作脂肪分解注射剂的溶剂,当应用于细胞时会导致坏死。一种新的脂肪分解制剂(NWL-10)仅含有纳米颗粒大小的多烯磷脂酰胆碱、甘草酸和麦芽糖,已被报道具有脂肪分解作用。然而,目前还没有数据表明 NWL-10 混合物是否会导致脂肪组织的细胞凋亡或坏死,而这种情况可能与报道的脱氧胆酸制剂一样,会引起更严重的副作用。

方法

将 3T3-L1 小鼠细胞和人脂肪组织来源的干细胞暴露于 NWL-10 混合物及其混合物的每种成分中,以研究细胞毒性、脂肪分解、坏死或凋亡作用。此外,还使用 Balb/C 小鼠动物模型通过生物发光监测和组织学检查来研究 NWL-10 对炎症反应的影响。

结果

当应用于两种细胞类型时,NWL-10 混合物显示出高度的脂肪分解作用,而没有细胞毒性作用。有趣的是,低浓度的 NWL-10 导致坏死,而高浓度的 NWL-10 则显示出一定数量的细胞凋亡。应用 NWL-10 的单一成分或两种成分混合物的各种组合均未导致任何细胞凋亡或坏死。此外,在小鼠模型中未观察到 NWL-10 的炎症作用。

结论

与目前可用的注射剂相比,NWL-10 混合物在脂肪组织的脂肪分解方面提供了有希望的结果,同时细胞凋亡和坏死的程度有限。这些初步的有希望的结果需要进一步进行基本和更详细的研究,以获得药物批准的必要条件。NWL-10 有可能成为未来脂肪分解注射剂的第二代产品。

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