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霉酚酸酯对(NZB×NZW)F1 小鼠皮肤狼疮红斑的影响。

Effects of mycophenolate mofetil on cutaneous lupus erythematosus in (NZB × NZW) F1 mice.

机构信息

Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, ROC.

出版信息

J Chin Med Assoc. 2013 Nov;76(11):615-23. doi: 10.1016/j.jcma.2013.07.010. Epub 2013 Aug 19.

Abstract

BACKGROUND

Few studies have evaluated the effects and precise molecular mechanism of mycophenolate mofetil (MMF) in the treatment of human cutaneous lupus erythematosus (CLE). Our findings shed light on the therapeutic effects of MMF in a UVB-induced NZB × NZW (NZBW) F1 CLE mouse model.

METHODS

Continuous MMF treatment (60 mg/kg/day) was administered up to Day 50 from the beginning of UVB induction (Day 0; 20 weeks old), as the pathologic features of CLE are present after 50 days. The therapeutic effects of MMF treatment in NZBW lupus mice were examined by comparing histopathological changes, lupus band test (deposition of immune complexes at the dermal-epidermal junction) and colocalization of autoantibodies with a dermal autoantigen Dsg3, and by evaluating the associations of local matrix metalloprotease activities.

RESULTS

MMF improved survival in the NZBW lupus mice from 35.7% to 81.8%. The proteinuria, blood urea nitrogen, and interleukin 6 levels were significantly reduced after MMF treatment. The dermal lymphocytic infiltration, deposition of immune complexes at the dermal-epidermal junction, colocalized autoantibodies with Dsg3, and epidermal matrix metalloprotease activity were also attenuated in MMF-treated NZBW F1 mice.

CONCLUSION

The results confirmed that MMF could substantially attenuate skin damage due to CLE in the NZBW F1 mouse model.

摘要

背景

鲜有研究评估霉酚酸酯(MMF)在治疗人类皮肤红斑狼疮(CLE)中的作用和确切的分子机制。我们的研究结果揭示了 MMF 在 UVB 诱导的 NZB×NZW(NZBW)F1 CLE 小鼠模型中治疗作用。

方法

从 UVB 诱导开始(第 0 天;20 周龄)到第 50 天(连续 MMF 治疗,每天 60mg/kg),给予持续 MMF 治疗,因为 CLE 的病理特征在 50 天后出现。通过比较组织病理学变化、狼疮带试验(真皮-表皮交界处免疫复合物沉积)和自身抗体与真皮自身抗原 Dsg3 的共定位,以及评估局部基质金属蛋白酶活性的相关性,来检测 MMF 治疗在 NZBW 狼疮小鼠中的疗效。

结果

MMF 将 NZBW 狼疮小鼠的存活率从 35.7%提高到 81.8%。MMF 治疗后蛋白尿、血尿素氮和白细胞介素 6 水平显著降低。真皮淋巴细胞浸润、真皮-表皮交界处免疫复合物沉积、与 Dsg3 共定位的自身抗体以及表皮基质金属蛋白酶活性在 MMF 治疗的 NZBW F1 小鼠中也减弱。

结论

结果证实,MMF 可显著减轻 NZBW F1 小鼠模型中 CLE 引起的皮肤损伤。

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