人胎盘来源的间充质干细胞移植对递增负荷训练诱导的POI大鼠卵巢功能的影响  

Effects of Human Placenta-derived Mesenchymal Stem Cell Transplantation on Ovarian Function in Rats with Incremental Load Training-induced POI

作　　者：杨璐 魏翠 李红兰 徐妍 YANG Lu;WEI Cui;LI Honglan;XU Yan(Department of Sport and Health Sciences,Nanjing Sport Institute,Nanjing 210014,Jiangsu,China;Institute of Regenerative Medicine,Sanhe(Nanjing)Biotechnology Co.,Ltd.,Nanjing 210031,Jiangsu,China;Nanjing Regenerative Medicine Engineering and Technology Research Center,Nanjing 210031,Jiangsu,China)

机构地区：[1]南京体育学院运动健康学院,中国江苏南京210014 [2]三和(南京)生物科技有限公司再生医学研究中心,中国江苏南京210031 [3]南京市再生医学工程技术研究中心,中国江苏南京210031

出　　处：《生命科学研究》2023年第2期114-127,138,共15页Life Science Research

基　　金：南京市生命健康科技专项-临床前沿突破项目(202110012)。

摘　　要：随着女性生育年龄的推迟,30~39岁早发性卵巢功能不全(premature ovarian insufficiency,POI)患者的治疗需求增加。先前的研究证实,不同组织来源的干细胞可以恢复POI小鼠的卵巢功能。本研究旨在探讨人胎盘间充质干细胞(human placenta-derived mesenchymal stem cell,hpMSC)移植治疗递增负荷训练诱导的POI的效果和潜在机制。首先,采用为期9周的递增负荷跑台训练建立POI大鼠模型;然后,通过尾静脉注射给予hpMSC移植治疗;最后,通过激素水平和组织学分析评估卵巢功能,利用hpMSC示踪、酶联免疫吸附试验(en-zyme linked immunosorbent assay,ELISA)、免疫印迹分析、免疫组织化学染色和实时荧光定量PCR评估损伤和修复的分子机制。结果显示,移植后的hpMSC定植在卵巢间质;hpMSC移植增加了卵母细胞的端粒长度,减少了氧化应激反应,下调了Bax(Bcl-2-associated X protein)和胱天蛋白酶-3(caspase-3)的蛋白质水平,与此同时,卵泡刺激素(follicle-stimulating hormone,FSH)的水平、FSH与黄体生成素(luteinizing hormone,LH)的比值(FSH/LH)下降,各级卵泡数量增加。实验结果表明,hpMSC移植可以修复递增负荷训练诱导的POI大鼠的卵巢损伤,改善卵巢功能。With the delay of female childbearing age,the need for treatment of premature ovarian insufficiency(POI)in women aged 30~39 is increasing.Previous studies confirmed that different tissue-derived stem cells could restore ovarian function of POI mice.The purpose of this study was to explore the efficacy and underlying mechanisms of human placenta-derived mesenchymal stem cell(hpMSC)transplantation for incremental load training-induced POI.After establishment of a POI rat model by 9-week treadmill training with incremental load,the POI rats were administered with hpMSCs by tail vein injection.Ovarian function was evaluated by detection of hormone levels and histological analysis.hpMSC tracking,enzyme linked immunosorbent assay(ELISA),Western-blot,immunohistochemistry staining,and real-time fluorescence quantitative PCR were used to assess the molecular mechanisms of ovarian function injury and repair.The results showed that hpMSCs colonized the ovarian stroma.hpMSC transplantation increased oocyte telomere length,reduced oxidative stress,downregulated Bcl-2-associated X protein(Bax)and caspase-3 expression levels.In addition,after transplantation,the follicle-stimulating hormone(FSH)levels and ratio of FSH to luteinizing hormone(FSH/LH)decreased,and the number of follicles at all stages increased.These results demonstrated that hpMSC transplantation could repair ovarian injury and improve ovarian function in incremental load training-induced POI rats.

关 键 词：早发性卵巢功能不全(POI) 间充质干细胞(MSC) 端粒 氧化应激 颗粒细胞 

分 类 号：Q492[生物学—生理学] R711.6[医药卫生—妇产科学]