口服他莫昔芬法建立ICR小鼠子宫腺肌病模型

目的使用口服他莫昔芬法建立ICR小鼠子宫腺肌病模型,并检测其病灶特征、动情周期、血管生成、子宫炎症等变化,以介绍和评价这一动物模型。方法新生ICR小鼠（15只）连续4 d滴喂他莫昔芬,并与同龄对照小鼠（15只）分别于42、85-95、135-145日龄处死,使用苏木素-伊红染色检测子宫病理改变;阴道脱落细胞法检测动情周期变化;免疫组化补体31（CD31）染色计算子宫微血管的密度、直径及所占面积比;逆转录-聚合酶链反应（RT-PCR）检测子宫缓激肽受体、神经激肽受体的基因表达。结果使用口服他莫昔芬法建立ICR小鼠子宫腺肌病模型的造模率为100%,且疾病严重程度随病程进展。部分给药小鼠可出现动情周期紊乱。85-95及135-145日龄给药小鼠子宫肌层微血管密度和面积比均高于对照小鼠（P〈0.05）。135-145日龄给药小鼠子宫缓激肽受体、神经激肽受体的基因表达较对照组明显升高（P〈0.05）。结论口服他莫昔芬法可方便、高效的建立腺肌病小鼠模型,出现腺肌病相关的血管生成、炎症状态、疼痛相关受体表达增高等特征,是研究腺肌病发生、发展的良好模型。

Establishment of an ICR Mouse Model of Adenomyosis by Oral Administration of Tamoxifen

Objective To establish an ICR mouse model of adenomyosis with tamoxifen and to characterize the adenomyosis nodules,estrus,angiogenesis and uterine inflammation in this animal model.Methods ICR mice with adenomyosis were induced by orally administration of tamoxifen on days 2～5 after birth.15 drug and 15 control mice were killed on day 42,day 85～95 and day 135～145,respectively.Hematoxylin and eosin（HE） staining was performed to examine the adenomyosis nodules.Estrous cycle was determined by the presence of a characteristic vaginal discharge.Microvessel density,diameter and the ratio of area in the uterus were assessed by immunohistochemistrial staining with CD31.The gene expression of bradykinin receptor-1（BKR-1） and neurokinin1 receptor（NK1-R） was detected by RT-PCR.Results All mice dosed with tamoxifen developed adenomyosis with an incidence rate of 100%.The microvessel density and the ratio of area in myometrium of experimental mice were significantly higher than those in the controls（P0.05）.In the uterus of 135～145 d drug mice,the mRNA expression of BKR-1 and NK1-R was significantly higher than that of controls（P0.05）.Conclusion The mouse model of adenomyosis induced by tamoxifen has abnormal angiogenesis,inflammation and pain related receptor expression in the uterus.Moreover,it is simple and effective to create this model,valuable for future adenomyosis research.