CAJ | 학술논문

目的探讨辛伐他汀对硬皮病小鼠模型胶原合成的影响.方法采用博来霉素诱导的动物模型,分早期给药组和硬化后给药组.用5 mg·kg-1·d-1辛伐他汀处理,用药4周后收集标本,采用HE染色观察皮损组织病理改变并测量表真皮厚度,比色法榆测皮损羟脯氨酸含量,并利用逆转录-聚合酶链反应(RT-PCR)方法检测小鼠硬皮病皮损前胶原(pro-COL1α1)mRNA的表达情况.结果早期给药组中,模型组与阴性对照组比较,小鼠真皮内胶原增粗,表真皮厚度和羟脯氨酸含量及pro-COL1α1 mRNA表达明显增加(P<0.01);而5 mg·kg-1·d-1辛伐他汀处理组较模型组小鼠真皮厚度变薄(P<0.05),羟脯氨酸含量降低(P<0.01),皮损pro-COL1α1 mRNA表达下降(P<0.05).硬化后给药组中,辛伐他汀处理组与空白对照组比较小鼠真皮厚度、羟脯氨酸含量均无明显改善,但pro-COL1α1 mRNA表达下降(P<0.05).结论早期予以辛伐他汀处理可以减轻博来霉素诱导的小鼠皮肤硬化程度.硬化后予以辛伐他汀处理则皮肤硬化改善不明显.
목적 탐토신벌타정대경피병소서모형효원합성적영향.방법 채용박래매소유도적동물모형,분조기급약조화경화후급약조.용5 mg·kg-1·d-1신벌타정처리,용약4주후수집표본,채용HE염색관찰피손조직병리개변병측량표진피후도,비색법유측피손간포안산함량,병이용역전록-취합매련반응(RT-PCR)방법검측소서경피병피손전효원(pro-COL1α1)mRNA적표체정황.결과 조기급약조중,모형조여음성대조조비교,소서진피내효원증조,표진피후도화간포안산함량급pro-COL1α1 mRNA표체명현증가(P<0.01);이5 mg·kg-1·d-1신벌타정처리조교모형조소서진피후도변박(P<0.05),간포안산함량강저(P<0.01),피손pro-COL1α1 mRNA표체하강(P<0.05).경화후급약조중,신벌타정처리조여공백대조조비교소서진피후도、간포안산함량균무명현개선,단pro-COL1α1 mRNA표체하강(P<0.05).결론 조기여이신벌타정처리가이감경박래매소유도적소서피부경화정도.경화후여이신벌타정처리칙피부경화개선불명현.
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 injec-tions 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 derma l 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 P0.05), 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 scle- rosis but not by that after the induction of sclerotic skin.