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局部应用环孢素A在原发性干燥综合征小鼠模型中的应用

Use of topical cyclosporin A in a primary Sjögren's syndrome mouse model.

作者信息

Tsubota K, Saito I, Ishimaru N, Hayashi Y

机构信息

Department of Ophthalmology, and the Oral Health Science Center, Tokyo Dental College, Chiba, Japan.

出版信息

Invest Ophthalmol Vis Sci. 1998 Aug;39(9):1551-9.

PMID:9699544
Abstract

PURPOSE

A new animal model, the NFS/sld mutant mouse, was used for primary Sjögren's syndrome to investigate the efficacy of topical and systemic cyclosporin A (CyA) in preventing inflammation of the exocrine glands.

METHODS

Cyclosporin A was applied topically (0.01% and 0.1%, three times a day) or administered orally (10 mg/kg and 100 mg/kg, once a day) to mice from 6 to 16 weeks of age, after which the mice were killed.

RESULTS

Topical CyA reduced lacrimal gland and submandibular gland inflammation without causing pathologic changes in other organs. Flow cytometry showed that CD44 expression of CD4 T cells from the submandibular lymph nodes was downregulated, whereas that of Mel14+ was upregulated. Using a reverse transcription-polymerase chain reaction assay, we determined that topical CyA significantly decreased the expression of mRNA of IL-2 and T-cell receptor-constant beta-chain.

CONCLUSIONS

Topical CyA may be clinically useful in reducing the lymphocyte infiltration of lacrimal glands associated with Sjögren's syndrome.

摘要

目的

一种新的动物模型——NFS/sld突变小鼠,被用于原发性干燥综合征,以研究局部和全身应用环孢素A(CyA)预防外分泌腺炎症的疗效。

方法

对6至16周龄的小鼠局部应用环孢素A(0.01%和0.1%,每日3次)或口服给药(10mg/kg和100mg/kg,每日1次),之后处死小鼠。

结果

局部应用CyA减轻了泪腺和下颌下腺炎症,且未引起其他器官的病理改变。流式细胞术显示,下颌下淋巴结CD4 T细胞的CD44表达下调,而Mel14+的表达上调。通过逆转录-聚合酶链反应分析,我们确定局部应用CyA显著降低了IL-2和T细胞受体恒定β链的mRNA表达。

结论

局部应用CyA在临床上可能有助于减少与干燥综合征相关的泪腺淋巴细胞浸润。

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