Lyz2+单核-巨噬细胞在多囊卵巢综合征小鼠子宫中的谱系示踪  

Lineage Tracing of Lyz2+Monocytes-macrophages in the Uterus of Polycystic Ovary Syndrome Mice

作　　者：刘美辰 李博雅 任萌萌[1,2,3] 杨婷婷 马萍 曹思甜[1] 马虹 裴秀英 张淑雅[1,2] LIU Meichen;LI Boya;REN Mengmeng;YANG Tingting;MA Ping;CAO Sitian;MA Hong;PEI Xiuying;ZHANG Shuya(School of Basic Medical,Ningxia Medical University,Yinchuan 750004,China;Key Laboratory of Fertility Preservation and Maintenance,Ministry of Education,Ningxia Medical University,Yinchuan 750004,China;Yinchuan Maternal and Children Health Care Hospital,Yinchuan 750001,China)

机构地区：[1]宁夏医科大学基础医学院,银川750004 [2]宁夏医科大学生育力保持教育部重点实验室,银川750004 [3]银川市妇幼保健院,银川750001

出　　处：《宁夏医科大学学报》2024年第3期223-229,共7页Journal of Ningxia Medical University

基　　金：宁夏回族自治区重点研发计划项目(2023BEG02004,2021BEG03040);宁夏医科大学校级课题(XZ2022003)。

摘　　要：目的在骨髓来源巨噬细胞谱系示踪小鼠上建立多囊卵巢综合征(polycystic ovary syndrome,PCOS)模型,通过谱系示踪方法揭示巨噬细胞在PCOS小鼠子宫中的分布特点。方法利用Cre/LoxP系统构建骨髓来源巨噬细胞谱系示踪小鼠,分别构建Td-tomato^(flox/flox)小鼠和Lyz2^(Cre)工具小鼠,使两者进行交配,得到Lyz2^(Cre)Tdtomato^(flox/flox)小鼠,其骨髓来源单核-巨噬细胞均被标记上红色荧光蛋白(Td-tomato),再通过来曲唑联合高脂饲料构建PCOS小鼠模型,通过免疫荧光多标结合激光共聚焦共定位方法检测PCOS小鼠子宫中巨噬细胞的分布及数量。结果成功构建了骨髓来源单核-巨噬细胞谱系示踪小鼠(Lyz2^(Cre)Td-tomato^(flox/flox)),并在谱系示踪小鼠上成功构建了PCOS小鼠模型。PCOS小鼠子宫的HE染色结果显示结构异常;免疫荧光多重标记检测发现,在PCOS小鼠子宫中巨噬细胞分布在子宫外膜、肌层、内膜,且M2型巨噬细胞数量增多(P<0.05)。结论本研究构建了肥胖型PCOS小鼠模型,发现骨髓来源的M2型巨噬细胞在PCOS小鼠子宫中增多。Objective To establish a polycystic ovary syndrome(PCOS)model on bone marrow-derived macrophage lineage tracing mice,and reveal the distribution of macrophages in the uterus of PCOS through lineage tracing.Methods The Cre/LoxP system was used to construct bone marrow-derived macrophage lineage tracer mice,specifically by mating Td-tomato^(flox/flox) mice with Lyz2^(Cre) tool mice to obtain Lyz2^(Cre) Td-tomato^(flox/flox).Red fluorescent protein(Td-tomato)was used to label bone marrow-derived monocytes and macrophages,followed by the construction of a PCOS mouse model using letrozole combined with high-fat feed.The distribution and number of macrophages in the mice uterus were then examined.Results A bone marrow-derived monocyte-macrophage lineage tracer mouse(Lyz2^(Cre) Td-tomato^(flox/flox))was successfully constructed,and a PCOS mouse model was also successfully established by using this lineage tracer mouse.The HE staining of the uterus of PCOS mice revealed structural abnormalities.Multiple labeling with immunofluorescence detection showed that macrophages in the uterus were distributed in the epimetrium,myometrium,and endometrium,with a significant increase in the number of M2 macrophages in the uterus of the PCOS group(P<0.05).Conclusion The obese PCOS mouse model was successfully established.The findings indicate a significant increase in bone marrow-derived M2 macrophages in the uterus of PCOS mice.

关 键 词：谱系示踪 多囊卵巢综合征 CRE/LOXP系统 骨髓来源巨噬细胞 

分 类 号：R711.6[医药卫生—妇产科学]