南方医科大学学报

南方医科大学学报 ›› 2018, Vol. 38 ›› Issue (11): 1318-.doi: 10.12122/j.issn.1673-4254.2018.11.07

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二甲基苯并蒽诱导外阴鳞状上皮内病变大鼠模型的建立

范艺巾，唐华均，刘瑶，李成志   

  • 出版日期:2018-11-20 发布日期:2018-11-20

Establishment of a rat model of dimethylbenzanthracene-induced vulvar squamous intraepithelial lesions

  • Online:2018-11-20 Published:2018-11-20

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摘要： 目的建立SD大鼠外阴鳞状上皮内病变动物模型。方法采用二甲基苯并蒽（DMBA）丙酮溶液制备外阴鳞状上皮内病变 动物模型，将70只雌性SD大鼠分成空白对照组（10只）、机械刺激组（10只）、丙酮组（10只）、机械刺激+DMBA丙酮实验组（模 型组，40只）；每周3次对各组SD大鼠外阴皮肤进行相应处理，实验处理14周，观察至18周。分别于6、8、10、12、14、18周在肉眼 及光镜下动态观察4组SD大鼠外阴皮肤变化情况；取空白对照组和模型组SD大鼠外阴皮肤，采用免疫组织化学染色及免疫印 迹法检测突变型p53（mtp53）和血管内皮生长因子（VEGF）蛋白的相对表达量，qRT-PCR 检测mtp53和VEGF mRNA的表达情 况。结果空白对照组、机械刺激组及丙酮组大鼠各个时期形态学及组织病理学变化无明显差异。模型组SD大鼠在第14周 70%出现了低级别鳞状上皮内病变改变，27.5%出现高级别鳞状上皮内病变改变，造模成功率达97.5%；免疫组化和Western blotting 检测结果显示，与空白对照组相比，模型组mtp53 和VEGF蛋白均有明显增加，差异具有统计学意义（P<0.05）。qRTPCR 结果显示，模型组大鼠外阴皮肤中mtp53和VEGF mRNA的表达均高于空白对照组，差异具有统计学意义（P<0.05）。结 论0.5% DMBA丙酮溶液联合单纯机械刺激可以诱导雌性SD大鼠建立外阴鳞状上皮内病变动物模型。

Abstract: Objective To establish a SD rat model of vulvar squamous intraepithelial lesions. Methods Seventy female SD rats were randomized into 4 groups, namely the blank control group (n=10), mechanical irritation group (n=10), acetone solution group (n=10), and mechanical irritation with DMBA acetone solution group (n=40, model group), and the corresponding treatments were administered 3 times a week for 14 weeks. The changes of the vulvar skin of the rats were observed regularly until the 18th week. The expression of mutant p53 (mtp53) and vascular endothelial growth factor (VEGF) proteins were detected using immunohistochemistry and Western blotting, and the expressions of mtp53 and VEGF mRNA were detected with qRT- PCR in the blank control group and model group. Results No significant differences were found in the morphological or histopathological changes of the skin among the blank control group, mechanical irritation group and acetone solution group. In the model group, low-grade squamous intraepithelial lesions (LSIL) occurred in 28 rats (70%) and high-grade squamous intraepithelial lesions (HSIL) in 11 rats (27.5%) at 14 weeks, with a success rate of 97.5% in inducing vulvar squamous intraepithelial lesions. Compared with the blank control group, the rats in the model group showed significantly increased expressions of mtp53 and VEGF at both the protein level (P<0.05) and the mRNA level (P<0.05). Conclusion DMBA in acetone solution combined with mechanical irritation can induce vulvar squamous intraepithelial lesions in female SD rats.