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在过敏性接触性皮炎小鼠模型中,局部应用纳米晶银乳膏可抑制炎性细胞因子并诱导炎性细胞凋亡。

Topical nanocrystalline silver cream suppresses inflammatory cytokines and induces apoptosis of inflammatory cells in a murine model of allergic contact dermatitis.

作者信息

Bhol K C, Schechter P J

机构信息

NUCRYST Pharmaceuticals Inc., 50 Audubon Road, Wakefield, MA 01880, USA.

出版信息

Br J Dermatol. 2005 Jun;152(6):1235-42. doi: 10.1111/j.1365-2133.2005.06575.x.

DOI:10.1111/j.1365-2133.2005.06575.x
PMID:15948987
Abstract

BACKGROUND

Nanocrystalline silver has both antimicrobial and anti-inflammatory properties. However, the exact mechanisms underlying these activities are not known.

OBJECTIVES

The objectives of this study were to assess the anti-inflammatory effects of nanocrystalline silver using a murine model of allergic contact dermatitis, compare the effects with those of tacrolimus and a high potency steroid, and to relate the effects to modulation of pro-inflammatory cytokines and apoptosis of inflammatory cells.

METHODS

Dermatitis was induced on the ears of BALB/c mice using dinitrofluorobenzene. Topical treatment, including vehicles, 1% nanocrystalline silver cream, tacrolimus ointment and a high potency steroid, was applied once a day for 4 days. Ear swelling was measured and the erythema was evaluated daily. After 4 days of treatment the mice were killed and samples from the ears were collected for histological and immunohistochemical examination, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labelling (TUNEL) staining and extraction of total RNA for reverse transcriptase polymerase chain reaction (RT-PCR).

RESULTS

Significant reductions of ear swelling, erythema and histopathological inflammation in mice ears were observed after 4 days of treatment with 1% nanocrystalline silver cream, tacrolimus ointment or a high potency steroid with no significant difference among them. Both RT-PCR and immunohistochemical staining of sections from ear biopsies demonstrated that nanocrystalline silver, tacrolimus and steroid significantly suppressed the expression of tumour necrosis factor (TNF)-alpha and interleukin (IL)-12. TUNEL staining demonstrated a significant increase in the numbers of apoptotic cells in material from the group treated with nanocrystalline silver when compared with that from groups treated with vehicle, tacrolimus or steroid.

CONCLUSIONS

This study demonstrates that nanocrystalline silver inhibits allergic contact dermatitis in mice, similar to steroid and tacrolimus. Nanocrystalline silver suppresses the expression of TNF-alpha and IL-12 and induces apoptosis of inflammatory cells; mechanisms by which nanocrystalline silver may exert its anti-inflammatory effects.

摘要

背景

纳米晶银具有抗菌和抗炎特性。然而,这些活性背后的确切机制尚不清楚。

目的

本研究的目的是使用过敏性接触性皮炎小鼠模型评估纳米晶银的抗炎作用,将其与他克莫司和高效类固醇的作用进行比较,并将这些作用与促炎细胞因子的调节和炎症细胞凋亡联系起来。

方法

使用二硝基氟苯在BALB/c小鼠耳部诱发皮炎。局部治疗,包括赋形剂、1%纳米晶银乳膏、他克莫司软膏和高效类固醇,每天应用一次,持续4天。每天测量耳部肿胀并评估红斑情况。治疗4天后处死小鼠,收集耳部样本进行组织学和免疫组织化学检查、末端脱氧核苷酸转移酶(TdT)介导的dUTP生物素缺口末端标记(TUNEL)染色以及提取总RNA用于逆转录聚合酶链反应(RT-PCR)。

结果

用1%纳米晶银乳膏、他克莫司软膏或高效类固醇治疗4天后,观察到小鼠耳部肿胀、红斑和组织病理学炎症显著减轻,它们之间无显著差异。耳部活检切片的RT-PCR和免疫组织化学染色均表明,纳米晶银、他克莫司和类固醇显著抑制肿瘤坏死因子(TNF)-α和白细胞介素(IL)-12的表达。TUNEL染色显示,与赋形剂、他克莫司或类固醇治疗组相比,纳米晶银治疗组材料中的凋亡细胞数量显著增加。

结论

本研究表明,纳米晶银抑制小鼠过敏性接触性皮炎,类似于类固醇和他克莫司。纳米晶银抑制TNF-α和IL-12的表达并诱导炎症细胞凋亡;这可能是纳米晶银发挥其抗炎作用的机制。

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