咪喹莫特诱导小鼠银屑病样动物模型的建立与评价
|
摘要
目的用咪喹莫特诱导的方法激发银屑病样模型并研究模型的形态学变化与稳定性。方法按体重将BALB/c小鼠随机分为2组:空白组和模型组,每组10只。模型组小鼠于背部涂抹咪喹莫特乳膏(涂抹面积2cm×2cm),空白组小鼠于背部涂抹凡士林,每次涂抹21 mg,1次/天,连续7 d。于末次涂药后,眼球取血,处死,背部皮肤固定于福尔马林中,用酶联免疫吸附法检测血清白细胞介素-17(IL-17)、白细胞介素-18(IL-18)、白细胞介素-22(IL-22)的含量,以免疫组织化学法检测皮损组织的增殖细胞核抗原(PCNA)、血管内皮生长因子(VEGF)、Toll样受体2(TLR2)的水平(灰度值)。结果模型组和空白组的血清IL-17分别为(0. 48±0. 24),(0. 27±0. 15) pg·m L~(-1);这2组的IL-18分别为(0. 48±0. 06),(0. 36±0. 09) pg·m L~(-1);这2组的IL-22分别为(0. 59±0. 12),(0. 46±0. 06) ng·m L~(-1);这2组的PCNA分别为62. 28±3. 23,135. 51±5. 07;这2组的VEGF分别为90. 16±3. 11,132. 31±4. 02;这2组的TLR2分别为65. 24±2. 03,142. 81±4. 26,上述指标,模型组与空白组比较,差异均有统计学意义(均P <0. 01)。结论该模型是一种有效的、稳定的、值得推广的银屑病模型。
Objective To stimulate the psoriatic-like model by using imiquimod-induced method to explore the morphological changes and stability of the model. Methods The BALB/c mice were randomly divided into 2 groups: blank group and an model group,with 10 mouse in each group. The mice in model group were coated with imiquimod 21 mg on the back( spread area 2 cm × 2 cm); mice in blank group were coated with vaseline 21 mg on the back,1 times a day,for 7 d. After the last application,the eye balls were sacrificed and the back skin were fixed in formalin. The serum interleukin 17( IL-17),interleukin 18( IL-18)and interleukin 22( IL-22) were detected by enzyme linked immunosorbent assay. The levels of the proliferating cell nuclear antigen( PCNA),vascular endothelial growth factor( VEGF) and Toll-like receptor( TLR2) were detected by immunohistochemistry( grey value). Results Serum IL-17 in model group and blank group were( 0. 48 ± 0. 24)and( 0. 27 ± 0. 15) pg · m L~(-1),respectively; IL-18 in the 2 groups were( 0. 48 ± 0. 06) and( 0. 36 ± 0. 09) pg·m L~(-1),respectively; IL-22 in the 2 groups were( 0. 59 ± 0. 12),( 0. 46 ± 0. 06) ng · m L~(-1),respectively; PCNA levels in the 2 groups were 62. 28 ± 3. 23,135. 51 ± 5. 07,and VEGF levels in the 2 groups were90. 16 ± 3. 11,132. 31 ± 4. 02; TLR2 levels in the 2 groups were 65. 24 ± 2. 03,142. 81 ± 4. 26,respectively. Comparison between blank group and model group,the difference of above factors had significantly( all P < 0. 01). Conclusion This model is an effective,stable,and worthwhile psoriasis model.
Objective To stimulate the psoriatic-like model by using imiquimod-induced method to explore the morphological changes and stability of the model. Methods The BALB/c mice were randomly divided into 2 groups: blank group and an model group,with 10 mouse in each group. The mice in model group were coated with imiquimod 21 mg on the back( spread area 2 cm × 2 cm); mice in blank group were coated with vaseline 21 mg on the back,1 times a day,for 7 d. After the last application,the eye balls were sacrificed and the back skin were fixed in formalin. The serum interleukin 17( IL-17),interleukin 18( IL-18)and interleukin 22( IL-22) were detected by enzyme linked immunosorbent assay. The levels of the proliferating cell nuclear antigen( PCNA),vascular endothelial growth factor( VEGF) and Toll-like receptor( TLR2) were detected by immunohistochemistry( grey value). Results Serum IL-17 in model group and blank group were( 0. 48 ± 0. 24)and( 0. 27 ± 0. 15) pg · m L~(-1),respectively; IL-18 in the 2 groups were( 0. 48 ± 0. 06) and( 0. 36 ± 0. 09) pg·m L~(-1),respectively; IL-22 in the 2 groups were( 0. 59 ± 0. 12),( 0. 46 ± 0. 06) ng · m L~(-1),respectively; PCNA levels in the 2 groups were 62. 28 ± 3. 23,135. 51 ± 5. 07,and VEGF levels in the 2 groups were90. 16 ± 3. 11,132. 31 ± 4. 02; TLR2 levels in the 2 groups were 65. 24 ± 2. 03,142. 81 ± 4. 26,respectively. Comparison between blank group and model group,the difference of above factors had significantly( all P < 0. 01). Conclusion This model is an effective,stable,and worthwhile psoriasis model.
引文
[1]NESTLE F O,KAPLAN D H,BARKER J.Psoriasis[J].N Engl JMed,2009,361(17):496-509.
[2]GUDJONSSON J E,JOHNDTON A,DYSON M,et al.Mouse models of psoriasis[J].J Invest Dermatol,2007,127(6):1292-1308.
[3]SANO S,CHEN K S,CLIFFORD J,et al.State3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model[J].Nature Med,2005,11(1):43-49.
[4]RAJAN N,LANGTRY J A.Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas[J].Clin Exp Dermatol,2006,31(1):140-141.
[5]FITS L V,MOURITS S,VOERMAN J S,et al.Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17axis[J].J Immunol,2009,182(9):5836-5845.
[6]LOWES M A,KIKUCHI T,FUENTES-DUCULAN J,et al.Psoriasis vulgaris lesion contain discrete populations of Th1 and Th17 T cells[J].Invest Dermatol,2008,128(5):1207-1211.
[2]GUDJONSSON J E,JOHNDTON A,DYSON M,et al.Mouse models of psoriasis[J].J Invest Dermatol,2007,127(6):1292-1308.
[3]SANO S,CHEN K S,CLIFFORD J,et al.State3 links activated keratinocytes and immunocytes required for development of psoriasis in a novel transgenic mouse model[J].Nature Med,2005,11(1):43-49.
[4]RAJAN N,LANGTRY J A.Generalized exacerbation of psoriasis associated with imiquimod cream treatment of superficial basal cell carcinomas[J].Clin Exp Dermatol,2006,31(1):140-141.
[5]FITS L V,MOURITS S,VOERMAN J S,et al.Imiquimod-induced psoriasis-like skin inflammation in mice is mediated via the IL-23/IL-17axis[J].J Immunol,2009,182(9):5836-5845.
[6]LOWES M A,KIKUCHI T,FUENTES-DUCULAN J,et al.Psoriasis vulgaris lesion contain discrete populations of Th1 and Th17 T cells[J].Invest Dermatol,2008,128(5):1207-1211.