摘要目的 探讨7,12?二甲基苯蒽( DMBA)诱导树鼩乳腺癌模型的可行性,并比较灌胃和乳腺注射两种给药方式建模的效果.方法 将40只树鼩随机分为灌胃组和乳腺注射组,每组20只.灌胃组:用食用植物油溶解的DMBA灌胃1次,15 mg／kg.乳腺注射组:向树鼩腹部一侧乳腺脂肪垫中注射以食用植物油溶解的DMBA,10 mg／kg,共注射3次.在给予DMBA的同时,开始在树鼩大腿外侧肌肉丰厚处注射醋酸甲羟孕酮,100 mg／kg,共注射5次.观察树鼩的成瘤和生存情况,对生成的病变组织行HE染色观察组织学形态,免疫组化染色检测雌激素受体( ER)、孕激素受体(PR)、细胞角蛋白5／6(CK5／6)和人表皮生长因子受体2(HER?2)的表达情况.结果 灌胃组死亡10只,存活10只,有4只树鼩成瘤,成瘤率为20.0%(4／20),乳腺癌成模率为10.0%(2／20),成瘤时间为(197.3± 15.1)d.乳腺注射组死亡8只,存活12只,有9只树鼩成瘤,成瘤率为45.0%(9／20),乳腺癌成模率为40.0%(8／20),成瘤时间为(71.8±19.0)d.两组死亡率和成瘤率差异无统计学意义(均P＞0.05),但乳腺注射组成模率高于灌胃组(P＜0.05),成瘤时间短于灌胃组(P＜0.01).灌胃组的病理类型有普通型导管增生、导管内乳头状瘤和导管原位癌.乳腺注射组病理类型有导管内乳头状瘤和导管原位癌.免疫组化染色显示,两组肿瘤组织中ER、PR和CK5／6均有不同程度阳性表达,HER?2阴性表达.结论 DMBA灌胃和乳腺注射两种方法均能成功建立树鼩乳腺癌模型,乳腺脂肪垫注射建模效果优于灌胃建模.

abstractsObjective To explore the feasibility of 7,12?dimethylbenz[ a] anthracene ( DMBA) induced tree shrew breast cancer model, and compare the effects of two administration modes by gavage and mammary gland injection. Methods A total of 40 tree shrews were randomly divided into two groups (20 animals per group): DMBA gavage group and mammary gland injection group. DMBA was dissolved in edible vegetable oil. For gavage group, tree shrews were administered with DMBA solutions (15 mg／kg) by gavage once a day. For mammary gland injection group, DMBA solution (10 mg／kg) was injected into the mammary fat pad of tree shrews, and the injection was performed for a total of 3 times. From the first administration of DMBA, medroxyprogesterone acetate (MPA, 100 mg／kg) was intramuscularly injected into the muscles of the lateral thighs of tree shrews at the same time, for a total of 5 times. The tumorigenesis and survival of tree shrews were monitored. The tumor histological morphology was observed by HE staining. The expression of estrogen receptor (ER), progesterone receptor ( PR), cytokeratin5／6 ( CK5／6) and human epidermal factor receptor?2 (HER?2) was detected by immunohistochemical staining.Results In the gavage group, there were 10 deaths, and 4 tree shrews developed mammary tumors with 20.0%( 4／20) tumor formation rate. The success rate of mammary cancer modeling was 10.0%(2／20), and the tumor formation time was 197.3±15.1 days. In the mammary gland injection group, there were 8 tree shrews died, and 9 tree shrews formed tumors with 45.0%( 9／20) tumor formation rate. The success rate of mammary cancer modeling was 40.0%(8／20), and the tumor formation time was 71.8±19.0 days. There was no significant difference in mortality and tumor formation rate (P＞0.05) between the two groups (all P＞0.05). However, in the mammary gland injection group, the success rate of mammary cancer modeling was significantly higher than that in the gavage group (P＜0.05), whereas the tumor formation time was markedly shorter than that in the gavage group ( P＜0.01). The pathological types in the gavage group included ductal hyperplasia, intraductal papilloma and ductal carcinoma in situ, while those in the breast injection group included intraductal papilloma and ductal carcinoma in situ. In both groups, immunohistochemical staining showed the negative expression of HER?2 but positive expression of ER, PR and CK5／6 with varying degrees. Conclusion Both the DMBA gavage and mammary gland injection can successfully establish the tree shrew breast cancer model, and the modeling effect of mammary gland injection is better than gavage.