过表达miR-21的骨髓间充质干细胞在化疗性卵巢早衰大鼠模型中的治疗潜能及机制Therapeutic potential and mechanism of bone marrow mesenchymal stem cells with over expression of miR-21 in rat models of chemotherapy-induced premature ovarian failure
李欣然;何援利;王雪峰;彭冬先;陈小莹;王清;付霞霏;
摘要(Abstract):
目的:探讨过表达miR-21的BMMSCs对化疗性卵巢早衰的治疗作用及可能机制。方法:采用分子生物学方法构建miR-21慢病毒表达载体(LV-miR-21)。使用LV-miR-21转染体外分离培养的大鼠BMMSCs,获得过表达miR-21的BMMSCs(miR-21-BMMSCs)。建立化疗性卵巢早衰大鼠模型,双侧卵巢注射miR-21-BMMSCs,分别于注射后第15天、30天、45天、60天分批处死大鼠。采用阴道涂片测定动情周期,卵巢称重,HE染色进行卵泡计数,化学发光法测定性激素水平,TUNEL法测定卵巢颗粒细胞凋亡率,qRT-PCR、Western blot法检测miR-21及PTEN、PDCD4的mRNA及蛋白水平。结果:双侧卵巢注射miR-21-BMMSCs后,化疗诱导的POF大鼠动情周期恢复率、卵巢重量、各级卵泡数和E2水平增加,而FSH水平及卵巢颗粒细胞凋亡率下降。此外,miR-21表达水平的上升伴随PTEN、PDCD4 mRNA及蛋白水平的下降。结论:过表达miR-21的BMMSCs能更有效地治疗化疗性卵巢早衰,可能与其调控靶基因PTEN、PDCD4密切相关。
关键词(KeyWords): microRNA-21;骨髓间充质干细胞;卵巢颗粒细胞;卵巢早衰;化疗
基金项目(Foundation): 国家自然科学基金资助项目(No:81300462)
作者(Authors): 李欣然;何援利;王雪峰;彭冬先;陈小莹;王清;付霞霏;
DOI: 10.13283/j.cnki.xdfckjz.2018.12.010
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