雷帕霉素通过抑制mTOR信号延长成年雌性大鼠卵巢的寿命  

Rapamycin extends the ovarian lifespan of adult female rats through suppressing mTOR signaling

作　　者：张杏梅[1,2] 罗丽莉[1] 傅玉才[3] 许锦阶[3] 栗丽[1] 刘炜娟[1] 

机构地区：[1]汕头大学医学院第一附属医院妇产科,广东汕头515041 [2]惠州市中心人民医院妇产科,广东惠州516001 [3]汕头大学医学院细胞衰老实验室,广东汕头515041

出　　处：《热带医学杂志》2013年第8期925-927,F0004,共4页Journal of Tropical Medicine

基　　金：国家自然科学基金(81070458)

摘　　要：目的探讨雷帕霉素对成年雌性大鼠卵泡发育及卵巢寿命的影响,并研究mTOR信号在其中的作用。方法将16只8周龄雌性SD大鼠随机分为对照组和雷帕霉素干预组,观察两组大鼠动情周期的变化;10周后取大鼠卵巢,组织切片经苏木精-伊红染色,计数不同发育阶段的各级卵泡数;用蛋白免疫印迹(Western-blot)检测卵巢中mTOR和其磷酸化的靶分子S6K的蛋白表达水平。结果雷帕霉素干预组大鼠健康卵泡数(225.0±16.2)显著多于对照组(178.4±5.3),差异有统计学意义(P<0.05)。其中原始卵泡数(132.5±13.7)是对照组(59.6±5.2)的2倍多,而窦状卵泡和闭锁卵泡数则明显低于对照组,差异均有统计学意义(P<0.01)。雷帕霉素干预组mTOR和P-P70S6K蛋白表达水平明显低于对照组,差异有统计学意义(P<0.05)。结论雷帕霉素可能通过抑制mTOR信号,从而抑制原始卵泡向发育卵泡转化,保存原始卵泡储备,由此使卵巢的寿命延长。Objective To study the effect of rapamycin on ovarian lifespan and investigate the role of mTOR signaling in the follicular development.Methods Female Sprague-Dawley rats （n=16） were randomly divided into normal control and rapamycin-treated groups.The estrous cycle patterns were determined by vaginal smears every day.Ovaries were collected from the rats after 10 weeks of treatment.Ovarian tissue sections were prepared and the hematoxylin and eosin staining was performed to examine the number of ovarian follicles at different developmental stages.Western blotting was performed to examine the expression of mTOR and its phosphorylated target P-P70S6K proteins in rat ovaries.Results The total number of healthy follicles was significantly higher in the rapamycin-treated rats than in the control rats （225.0±16.2 vs.178.4±5.3,P＆lt;0.05）.The number of primordial follicles in the rapamycin-treated group was two times larger than those in the control group （132.5±13.7 vs.59.6±5.2,P＆lt;0.001）.The numbers of mature and atretic follicles in the rapamycin treated group were lower than those in the control group （P＆lt;0.01）.Western blotting result showed that the expression of mTOR and P-P70S6K in the rapamycin treated group was significantly decreased compared to the control group （P＆lt;0.05）.Conclusion Rapamycin may inhibit the transition from primordial to developing follicles and preserve the reserve of follicle pool,thus extending the ovarian lifespan of female rats through suppressing mTOR signaling.

关 键 词：雷帕霉素 MTOR 卵巢寿命 卵泡发育 

分 类 号：R392.2[医药卫生—免疫学]