恒河猴自发性盆腔器官脱垂作为研究人盆腔器官脱垂理想模型的综合评价

作     者：李雅倩 刘健 张也 毛萌 王宏 马懿迪 陈志刚 张又月 廖成敏 常晓青 高倩倩 郭建宾 叶扬 艾方方 刘旭东 赵晓悦 田维杰 杨华 季维智 谭韬 朱兰 Yaqian Li;Jian Liu;Ye Zhang;Meng Mao;Hong Wang;Yidi Ma;Zhigang Chen;Youyue Zhang;Chengmin Liao;Xiaoqing Chang;Qianqian Gao;Jianbin Guo;Yang Ye;Fangfang Ai;Xudong Liu;Xiaoyue Zhao;Weijie Tian;Hua Yang;Weizhi Ji;Tao Tan;Lan Zhu

作者机构：Medical Science Research Centerthe State Key Laboratory for ComplexSevereand Rare DiseasesPeking Union Medical College HospitalChinese Academy of Medical Science and Peking Union Medical CollegeBeijing 100730China State Key Laboratory of Primate Biomedical ResearchInstitute of Primate Translational MedicineKunming University of Science and TechnologyKunming 650500China Department of Obstetrics and GynecologyNational Clinical Research Center for Obstetric&Gynecologic Diseasesthe State Key Laboratory for ComplexSevereand Rare Diseasesthe State Key Laboratory of Common Mechanism Research for Major DiseasesPeking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100730China Department of Obstetrics and GynecologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450000China Department of Obstetrics and GynecologyBeijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Obstetrics and GynecologyXuanwu HospitalCapital Medical UniversityBeijing 100053China Department of GynecologyGuizhou Provincial People’s HospitalMedical College of Guizhou UniversityGuiyang 550002China 

出 版 物：《Science Bulletin》 (科学通报（英文版）)

年 卷 期：2023年第68卷第20期

页      面：2434-2447,M0006页

核心收录：

学科分类：1002[医学-临床医学] 100211[医学-妇产科学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(82171620 and 81830043) the National Key R&D Program of China(2021YFC2701403 and 2018YFC2002201) the National High Level Hospital Clinical Research Funding(2022-PUMCH-A-205 and 2022-PUMCH-A-114) 

主　　题：盆腔器官脱垂 临床前研究 生化改变 恒河猴 动物模型 细胞外基质 弹力纤维 成纤维细胞 

摘      要：盆腔器官脱垂严重影响女性的生活质量且其治疗的并发症严重.开发新疗法须在临床前研究中对其免疫反应和安全性进行评估.但多数四足动物的解剖结构和病理变化与人相差较大,目前缺乏合适的动物模型.本研究对72只老年恒河猴进行了体格检查,发现恒河猴自发性盆腔器官脱垂的发生率与人相似.作者选取了5只正常恒河猴和4只脱垂恒河猴的阴道组织进行进一步分析.Verhoeff-van Gieson染色表明,与正常恒河猴相比,恒河猴脱垂阴道的弹力纤维含量明显降低.免疫组化结果表明,恒河猴脱垂阴道的平滑肌束紊乱,大平滑肌束的数量明显低于正常恒河猴.天狼星红染色提示恒河猴脱垂阴道中Ⅰ型和Ⅲ型?原蛋白的比值明显降低.恒河猴脱垂阴道的组织学形态和生化改变与人脱垂相似.作者进一步构建了恒河猴脱垂后阴道的单细胞转录组图谱,对比分析显示人和恒河猴的阴道具有相似的细胞组成.差异基因分析提示细胞外基质失调和免疫紊乱是保守的分子机制.成纤维细胞和巨噬细胞的相互作用可能在人和恒河猴脱垂中都起到重要作用.综上,该研究对恒河猴自发性脱垂进行了综合评估并表明其是盆腔器官脱垂研究的合适动物模型.