解放军医学杂志2017,Vol.42Issue(9):759-763,5.DOI:10.11855/j.issn.0577-7402.2017.09.02
慢病毒介导的miR-21对化疗所致大鼠卵巢早衰的治疗作用
Therapeutic effect of lentivirus-mediated miR-21 on chemotherapy-induced premature ovarian failure in rats
摘要
Abstract
Objective To explore the therapeutic potential of miR-21 in rat model of chemotherapy-induced premature ovarian failure (POF).Methods Lentivirus-mediated miR-21 (LV-miR-21) was constructed successfully in vitro with molecular biology methods.Rats were divided into 4 groups named control group,model group,blank vector group and miR-21 group.Rat models of chem0therapy-induced POF were established in the latter 3 groups by intraperitoneal injection ofcytoxan (CTX).Bilateral ovaries of rats in miR-21 group were injected with LV-miR-21,of rats in blank vector group were injected with lentivirus vector,and rats in model group received no treatment.At 1,15,30,45 and 60 days after the last injection,blood sample was collected,the rats were then sacrificed and the ovaries were removed.The estrous cycle was observed by vaginal smears.The E2 level was detected by chemiluminescent immunoassay,and the follicle stimulating hormone (FSH) level was detected by homologous double antibody radiation immunoassay.Ovary weights were measured,and the follicle count was conducted through observing paraffin section under microscope.The apoptosis of ovarian granulosa cells was analyzed by TUNEL assay.Results During 15-30 days,30-45 days and 45-60 days after the last injection,regular estrous cycle was recovered respectively in 8,5 and 3 rats in miR-21 group.At the 15th,30th,45th and 60th day after the last injection,the E2 level was higher in miR-21 group than in model group and blank vector group,but the FSH level showed the opposite trend (P=0.000).At the 45th and 60th day after the last injection,the follicle numbers at all stages increased markedly in miR-21 group than in model group and blank vector group (P=0.000).At the 30th,45th and 60th day after the last injection,the ovary weights were higher in miR-21 group than in model group and blank vector group.At the 15th,30th,45th and 60th day after the last injection,the apoptosis rate of ovarian granulosa cell were significantly lower in miR-21 group than in model group and blank vector group (P=0.000).Conclusion Up-regulation of miR-21 expression may partly recover the ovarian structure and function damaged by CTX.关键词
microRNA-21/卵巢早衰/环磷酰胺/慢病毒/颗粒细胞Key words
microRNA-21/premature ovarian failure/cyclophosphamide/lentivirus/granulosa cells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..慢病毒介导的miR-21对化疗所致大鼠卵巢早衰的治疗作用[J].解放军医学杂志,2017,42(9):759-763,5.基金项目
国家自然科学基金青年基金(81300462) (81300462)
广东省科技计划项目(2013B021800145)This work was supported by the National Natural Science Foundation of China (81300462),and the Science and Technology Planning Project of Guangdong Province (2013B021800145) (2013B021800145)