现代妇产科进展2017，Vol.26Issue(9)：661-665,5.DOI:10.13283/j.cnki.xdfckjz.2017.09.003
miR-21调控PTEN及PDCD4基因治疗化疗性卵巢早衰
Lentivirus-mediated miR-21 alleviates cyclophosphamide-induced ovary damage by tar-geting PTEN and PDCD4 genes
摘要
Abstract
Objective:To investigate the potential therapeutic effect and the possible mechanisms of miR-21 in chemotherapy-induced premature ovarian failure ( POF) rats. Meth-ods:Lentivirus-mediated miR-21(LV-miR-21) was constructed in vitro. Rats were randomly di-vided into 4 groups, named control group, model group, lentivirus ( LV ) group and miR-21 group. Rat models of chemotherapy-induced POF were established by intraperitoneal injection of cyclophosphamide ( CTX ) . After the successful establishment of chemotherapy-induced POF model,bilateral ovaries of miR-21 group were injected with lentivirus-mediated miR-21. At the day 1,15,30,45 and 60 after the last injection,rats were killed in batch. Estrous cycle changes were detecting. Chemiluminescence and radioimmunoassay were used to determine the sexual hormone levels. The ovary weights were measured by scale and the follicles were counted under microscopy. The apoptosis of ovarian granulosa cells was analyzed by TUNEL assay. The mRNA and protein levels of phosphatase and tensin homolog on chromosome ten ( PTEN ) and pro-grammed cell death 4 (PDCD4) were detected using qRT-PCR and Western blot,respectively.Results:LV-miR-21 was constructed successfully in vitro. At the end of the experiment,estrous cycle of 64％ (16/25) rats in miR-21 group recovered. At 15,30,45 and 60 days after last in-jection,E2 level and granulosa cells apoptosis rates of miR-21 group were higher than model group and LV group (P=0. 000). Meanwhile,FSH level and mRNA and protein levels of PTEN,PDCD4 were lower than that of model and LV groups (P=0. 000). At 30,45,60 days after last injection,ovary weights of miR-21 group were significantly increased compared with model and LV groups,and were decreased compared with control group (P=0. 000). At 45 and 60 days after last injection,the number of developing follicles in miR-21 group was higher than model and LV groups ( P=0 . 000 ) . Conclusions:The mechanism of therapeutic potential of LV-miR-21 may involve down-regulated expression of PTEN and PDCD4 targeted by miR-21 .关键词
microRNA-21/卵巢早衰/环磷酰胺/卵巢颗粒细胞/慢病毒/PTEN/PDCD4Key words
MicroRNA-21/Premature ovarian failure/Cyclophosphamide/Granulosa cell/Lentiviruses/PTEN/PDCD4分类
医药卫生引用本文复制引用
李欣然,何援利,王雪峰,彭冬先,陈小莹,王清,付霞霏..miR-21调控PTEN及PDCD4基因治疗化疗性卵巢早衰[J].现代妇产科进展,2017,26(9):661-665,5.基金项目
国家自然科学基金(No:81300462) （No:81300462）
广东省科技计划项目(广东省科技攻关计划)(No:2013B021800145) （广东省科技攻关计划）
