人源异种皮下注射移植法建立子宫内膜异位症纤维化裸鼠模型的评价  

Evaluation of a nude mouse model of endometriosis fibrosis via the human xenograft subcutaneous transplantation method

作　　者：周雪[1,2] 万贵平 张真真[1,2] ZHOU Xue;WAN Guiping;ZHANG Zhenzhen(Nanjing University of Chinese Medicine Affiliated Hospital of Integrated Traditional Chinese and Western Medicine,Nanjing 210028,China;Jiangsu Province Academy of Traditional Chinese Medicine,Nanjing 210028)

机构地区：[1]南京中医药大学附属中西医结合医院,南京210028 [2]江苏省中医药研究院,南京210028

出　　处：《中国比较医学杂志》2024年第8期19-26,共8页Chinese Journal of Comparative Medicine

基　　金：国家自然科学基金面上项目(82074319,82174420);江苏省中医药研究院自主科研项目(BM2018024-2019007)。

摘　　要：目的评估人源子宫内膜异位症纤维化裸鼠模型建立的可行性,确定子宫内膜间充质干细胞是否参与诱导子宫内膜异位症纤维化。方法收集人源子宫内膜标本4例,采用皮下注射的方式1∶3移植到12只BABL/c裸鼠体内。记录病灶皮表形态及体积变化,移植后第15天处死裸鼠,观察病灶形态及其与腹壁周围粘连情况,HE染色评判造模结果,Masson染色评定纤维化程度,免疫荧光追踪子宫内膜间充质干细胞在子宫内膜异位症纤维化进程中的作用。结果裸鼠异位病灶体积随时间增长,呈局限性、囊泡样改变,与腹壁粘连紧密,镜下可见子宫内膜样腺体、胶原纤维沉积,造模成功率为83.4%,造模后病灶胶原纤维容积分数显著升高(P<0.01),共聚焦成像提示子宫内膜间充质干细胞(SUSD2^(+))可在体内向肌成纤维细胞(α-SMA^(+))分化。结论人源异种皮下注射移植的方法建立的裸鼠模型符合子宫内膜异位症纤维化的病变特点,操作简单,可行性高,此外体内观察到子宫内膜间充质干细胞参与诱导子宫内膜异位症纤维化形成,为进一步探究其发病机制提供较好的模型参考。Objective To assess the feasibility of establishing a nude mouse model of endometriosis fibrosis of human origin and to determine whether endometrial mesenchymal stem cells are involved in inducing endometriosis fibrosis.Methods Four endometrial tissue specimens were collected and transplanted 1∶3 into 12 BABL/c nude mice by subcutaneous injection.The morphology and volume of the lesions were recorded.The nude mice were sacrificed on the 15th day after transplantation to observe the morphology of the lesions and their adhesion to the periphery of the abdominal wall.HE staining was used to judge the result of modelling,Masson staining was used to assess the extent of fibrosis,and immunofluorescence was used to track the role of endometrial mesenchymal stem cells in the fibrotic process of endometriosis.Results The volume of ectopic lesions in nude mice increased over time and showed restricted,vesicular-like changes.The tight adhesion of the lesions to the abdominal wall,endometrioid glands,and collagen fiber deposition were seen microscopically.The success rate of the modelling was 83.4%,and the collagen fiber volume fraction of the lesions was significantly higher after modelling(P<0.01).Confocal imaging suggested that endometrial mesenchymal stem cells(SUSD2^(+))differentiated into myofibroblasts(α-SMA^(+))in vivo.Conclusions The nude mouse model established by human allogeneic transplantation via subcutaneous injection was consistent with the lesion characteristics of endometriosis fibrosis.The modelling method is simple and feasible and provides a better reference model for further investigating the pathogenesis of endometriosis fibrosis.In addition,in vivo observations using the model indicated that endometrial mesenchymal stem cells are involved in inducing the formation of endometriosis fibrosis.

关 键 词：子宫内膜异位症 动物模型 异种移植 纤维化 BABL/c裸鼠 子宫内膜间充质干细胞 

分 类 号：R-33[医药卫生]