文章摘要
周 咏,许 丽,肖 月,窦晓卫,李 晶.雷帕霉素对肥胖小鼠卵巢功能的影响[J].南京医科大学学报,2020,(9):1245~1251
雷帕霉素对肥胖小鼠卵巢功能的影响
Effects of rapamycin on ovarian function in obese mice
投稿时间:2019-09-10  
DOI:10.7655/NYDXBNS20200902
中文关键词: 雷帕霉素  肥胖  卵巢
英文关键词: rapamycin  obesity  ovary
基金项目:中国博士后科学基金项目(2018M640502)
作者单位
周 咏 南京医科大学生殖医学国家重点实验室江苏 南京 211166 
许 丽 南京医科大学生殖医学国家重点实验室江苏 南京 211166 
肖 月 南京医科大学生殖医学国家重点实验室江苏 南京 211166 
窦晓卫 南京医科大学生殖医学国家重点实验室江苏 南京 211166 
李 晶 南京医科大学生殖医学国家重点实验室江苏 南京 211166 
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中文摘要:
      目的:研究雷帕霉素对母源性肥胖导致的卵巢功能异常的干预作用以及药物的安全性评估。方法:建立一种高脂饮食的雌性肥胖小鼠模型,然后随机分为注射雷帕霉素的处理组和注射PBS的对照组,24周后统计其排卵数目,收集卵母细胞进行纺锤体免疫荧光染色,以评估雷帕霉素对肥胖小鼠排卵功能及卵母细胞质量的影响,并通过蛋白免疫印迹分析和RT?qPCR分析检测卵巢相关基因在蛋白和mRNA表达水平的变化。结果:雷帕霉素处理的肥胖小鼠体重下降,其卵巢磷酸化核糖体蛋白(phosphorylated ribosomal protein 6,P?rps6)和磷酸化起始因子4E结合蛋白(phosphorylated 4E binding protein 1,P?4EBP1)的表达明显降低,且超排的卵母细胞数目与对照相比有增加趋势,但卵母细胞纺锤体染色结果显示卵母细胞质量无明显差异;处理后的卵巢肿瘤坏死因子(tumor necrosis factorα,TNF?α)的mRNA表达水平增加;血清中雌激素和促卵泡激素都无明显变化。结论:雷帕霉素有改善排卵功能的趋势,尚未发现对卵母细胞质量有明显影响,为未来研究雷帕霉素对肥胖女性生育力的影响提供了实验基础。
英文摘要:
      Objective:This study aims to observe the intervention effect of rapamycin on ovarian dysfunction caused by maternal obesity and evaluate the safety of drugs. Methods:A female obesity mice model with high fat diet was established and then randomly divided into the treatment group injected with rapamycin and the control group injected with PBS. After 24 weeks,the number of ovulations was counted and the oocytes were collected for spindle operation. Immunofluorescence staining was used to evaluate the effect of rapamycin on ovulation function and oocyte quality in obese mice,and the expression of ovarian?related genes in protein and mRNA was detected by Western blot and RT?qPCR. Results:The weight of ovarian in rapamycin treated mice decreased. Expression of phosphorylated ribosoma lprotein(P?rps6) and the phosphorylated 4E binding protein1P(P?4EBP1) was significantly decreased in rapamycin?treated obese mice,and the number of superoved oocytes increased compared with the control. But results of the oocyte spindle staining showed no significant difference in oocyte quality between two groups. The mRNA expression level of tumor necrosis factor?α(TNF?α) in the ovary was increased after rapamycin treatment. There were no significant changes in serum estrogen and follicle stimulating hormone between two groups. Conclusion:Rapamycin has a tendency to improve ovulation function by inhibiting the mTOR signaling pathway. It was not found that rapamycin had a significant effect on oocyte quality. This study provided experimental basis for research of rapamycin on fertility in obese women in the future.
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