目的 探讨间充质干细胞外泌体(MSCs-Exos)是否通过PI3K/Akt/FOXO3a信号通路改善去卵巢大鼠的卵巢功能.方法 30只雌性大鼠随机分为假手术组、模型组和外泌体干预组,每组10只,建立去卵巢大鼠模型,尾静脉注射MSCs-Exos进行干预,第5周,采集血液和卵巢组织,ELISA方法检测血清雌二醇(E2)、抗苗勒氏激素(AMH)和卵泡刺激素(FSH)水平,qRT-PCR 和 Western blot 检测卵巢组织 Nanos3、Nobox、LHX8 以及 PI3K/Akt/FOXO3a信号通路基因及蛋白表达.结果 MSCs-Exos显著提高去卵巢大鼠血清雌二醇(E2)、抗苗勒氏激素(AMH)和卵泡刺激素(FSH)水平(P＜0.05);增加去卵巢大鼠卵巢卵泡数量(P＜0.05);促进去卵巢大鼠卵巢组织卵泡发生相关的Nanos3、Nobox、LHX8和LIN28a的mRNA和蛋白表达(P＜0.05);提高去卵巢大鼠卵巢组织PI3K、p-Akt、p-GSK3β和p-FOXO3a蛋白表达(P＜0.05).结论 MSCs-Exos可能通过PI3K/Akt/FOXO3a途径调节卵泡发生和卵母细胞生长继而改善卵巢功能.
Effect and possible mechanism of mesenchymal stem cell exosomes on ovarian function in ovariectomized rats
Objective To investigate whether mesenchymal stem cell exosomes(MSCs-exos)improve ovarian function in ovariectomized rats through PI3K/Akt/FOXO3a signaling pathway.Methods Thirty female rats were randomly divided into sham group,model group and exosome intervention group,with 10 rats in each group.The ovariectomized rat model was established,and MSCs-Exos was injected into the tail vein for intervention.At the 5 th week,blood and ovarian tissue were collected,and serum estradiol(E2),anti-Muehler hormone(AMH)and follicle-stimulating hormone(FSH)levels were detected by ELISA method.The expression of Nanos3,Nobox,LHX8 and PI3K/Akt/FOXO3a signaling pathway genes and proteins in ovarian tissue were detected by qRT-PCR and Western blot.Thirty female rats were randomly divided into sham group(n=10),model group(n=10)and exosome intervention group(n=10).Through the establishment of ovariectomized rat model,MSCs-exos was injected into caudal vein for intervention.At the 5th week,blood and ovarian tissues were collected for analysis.Levels of estradiol(E2),anti-Muellerian hormone(AMH)and follicle-stimulating hormone(FSH)in serum were detected by ELISA.The expressions of Nanos3,Nobox,LHX8 and PI3K/Akt/FOXO3a signaling pathway mRNA and protein in ovarian tissue were detected by qRT-PCR and Western blot.Results MSCs-exos significantly increased the levels of estradiol(E2),anti mullerian hormone(AMH)and follicle stimulating hormone(FSH)in serum of ovariectomized rats(P＜0.05).The number of ovarian follicles in ovariectomized rats was increased(P＜0.05).The expressions of Nanos3,Nobox,LHX8 and LIN28a related to ovarian folliculogenesis mRNA and protein were increased(P＜0.05).The expressions of PI3K,p-Akt and p-GSK3β and p-FOXO3a were increased(P＜0.05).Conclusion MSCs-Exos may regulate follicular genesis and oocyte growth through the PI3K/Akt/FOXO3a pathway to improve ovarian function.
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