关键词: 硬皮病;小鼠;动物模型;辛伐他汀

Abstract:

Objective To study the effect of simvastatin on the mouse model of sclerotic skin. Methods A total of 44 mice were divided into two groups, i.e., early administration group （n = 24） and post-induction administration group （n = 20）, and the former was classified into three subgroups, including negative group, model group and simvastatin-treated group, and the latter into two groups, namely blank control group, simvastatin-treated group. The mouse model of sclerotic skin was established by local injections of bleomycin in the back of BALB/c mice. Simvastatin was administered by gavage at a dose of 5 μg per kilogram body weight per day for 4 weeks to mice at the same time when bleomycin was injected in the early group or after 4-week bleomycin injection in the post-induction group. Skin sections were prepared 24 hours after the last administration of simvastatin for histopathological examination and measurement of dermal thickness with HE staining, determination of hydroxyproline content via colorimetry, and mRNA expression of procollagen α1 （Ⅰ） by RT-PCR. Results In the early administration group, a significant increment was observed in the diameter of dermal collagen, skin thickness, and hydroxyproline content in model group compared with the negative control group （all P < 0.01）, whereas decreased dermal thickness, hydroxyproline content and mRNA expression of procollagen α1 （Ⅰ） were noticed in simvastatin-treated group in comparison with the model group （P < 0.05, 0.01 and 0.05, respectively）. No obvious improvement was achieved in dermal thickness or hydroxyproline content in simvastatin-treated group compared with blank control group （both P > 0.05）, but the mRNA expression of procollagen α1 （Ⅰ） was inhibited in the former group （P < 0.05）. Conclusion Skin sclerosis is relieved significantly by administration of simvastatin at the induction of sclerosis but not by that after the induction of sclerotic skin.

Key words: scleroderma ,systemic;Simvastatin;Model, animal;Bleomycin