依托泊苷对实验性银屑病的治疗作用  

Therapeutic effect of etoposide on experimental psoriasis

作　　者：谢青[1] 王进[2] 王菊英[2] 颜会兰[1] 李应全[2] 

机构地区：[1]山东大学齐鲁医院药学部,山东济南250012 [2]山东大学医学院药理学研究所,山东济南250012

出　　处：《中国药理学与毒理学杂志》2008年第6期440-445,共6页Chinese Journal of Pharmacology and Toxicology

基　　金：山东省卫生厅科技发展基金(2005HW084)~~

摘　　要：目的观察依托泊苷对银屑病的治疗作用并初步探讨其作用机制。方法采用雌激素周期小鼠阴道上皮细胞有丝分裂模型及小鼠尾鳞片表皮模型,分别观察依托泊苷对小鼠阴道上皮细胞有丝分裂和尾鳞片表皮颗粒层形成的影响;酶联免疫吸附实验测定血清中白细胞介素2(IL-2)含量,放射免疫法测定血清肿瘤坏死因子α(TNFα-)和IL-10含量。结果依托泊苷5,10和20 m.gkg-1可显著促进小鼠尾鳞片表皮颗粒层形成,有颗粒细胞层的鳞片数从对照组(7.2±1.8)%分别升至(13.9±2.4)%,(15.7±2.1)%及(18.2±2.6)%;明显抑制小鼠阴道上皮细胞有丝分裂,有丝分裂指数从模型组(23.7±2.4)%分别降至(18.9±1.3)%,(15.6±2.0)%及(11.4±1.4)%。依托泊苷10和20 m.gkg-1可明显降低雌激素周期小鼠血清TNFα-水平,对IL-10水平无明显影响;依托泊苷5,10和20 m.gkg-1可降低尾鳞片表皮模型小鼠血清IL-2水平。结论依托泊苷对实验性银屑病具有治疗作用,该作用可能与其促进颗粒层细胞分化、抑制表皮细胞增殖并降低血清TNFα-和IL-2水平有关。AIM To investigate the therapeutic effect of etoposide on the experimental psoriasis and to explore the possible mechanism. METHODS The estrus cycle model mice with vaginal epithelium mitosis and mouse tail scaled epidermis model were used to evaluate the effects of etoposide on the epithelial cell mitosis and the granular layer formation. The serum interleukin-2 （IL-2） level was measured by using ELISA, while the serum levels of the tumor necrosis factor-α （TNF-α） and IL^-10 were determined by radioimmunoassay. RE- SULTS Etoposide （5, 10 and 20mg·kg^-1） promoted the formation of granular layers in the tail scaled epidermis, and inhibited the mitosis of vaginal epithelial cells in mice. Compared with the normal group, the numbers of the scale with granular layer in etoposide 5, 10 and 20 mg·kg^-1 groups increased from （7.2 ± 1.8 ） % to （13.9±2.4）%, （15.7 ±2. 1）% and （ 18.2 ± 2.6 ） %, respectively, while the mito sis index decreased from （ 23.7 ± 2.4 ） % to （18.9±1.3）%, （15.6 ±2.0）% and （11.4 ±1.3 ） % , respectively. Etoposide （ 10 and 20 mg·kg^-1） significantly decreased the serum TNF-αlevel in estrus cycle model mice with vaginal epithelium mitosis, while no effect was observed on the serum IL^-10 level. Etoposide （5, 10 and 20mg·kg^-1 ） markedly decreased the serum IL-2 level in mouse tail scaled epidermis model. CONCLUSION Etoposide has therapeutic effect on experimental psoriasis, which may be associated with its promotion on granular layer cell differentiation, inhibition of the epidermal cell hyperplasia, and decrease of serum levels of TNF-α and IL-2.

关 键 词：依托泊苷 银屑病 有丝分裂指数 肿瘤坏死因子 白细胞介素2 白细胞介素10 

分 类 号：R96[医药卫生—药理学]