PI3K信号通路激活对PCOS大鼠生殖相关内分泌指标的影响
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摘要
目的探讨PI3K信号通路激活对多囊卵巢(PCOS)大鼠生殖内分泌指标的影响。方法雌性SD大鼠随机分为参照组、模型组与干预组,各10只,除参照组外,均运用脱氢表雄酮(DHEA)建立PCOS大鼠模型。造模成功后,干预组在大鼠颈背部皮下注射利拉鲁肽,模型组、参照组则给予同剂量生理盐水。干预结束后10 h,观察各组卵巢组织形态变化;测定各组血清孕激素(P)、睾酮(T)、空腹血糖(FPG)、PI3K mRNA表达水平、AKT蛋白、磷酸化蛋白激酶B(p-AKT)活性。结果模型组卵巢结构紊乱,近包膜下见多个囊性扩张卵泡,部分卵泡内无卵母细胞,且放射冠消失,可见颗粒细胞层数减少,少见黄体;干预组颗粒细胞层较模型组增多,卵泡膜细胞层变薄,见成熟卵泡,黄体数量较模型组多。参照组与干预组血清P和FPG水平无显著差异,且均与模型组有显著差异,3组血清T水平大小顺序为参照组<干预组<模型组(P <0.05)。模型组PI3K m RNA、AKT蛋白、p-AKT蛋白表达水平低于其他两组(P <0.05);干预组仅PI3K mRNA表达水平高于参照组(P <0.05),而AKT蛋白和p-AKT蛋白表达水平与参照组相近(P> 0.05)。结论利拉鲁肽可通过激活PCOS大鼠PI3K信号通路,抑制雄激素表达,上调孕激素水平,并调节糖代谢,促排卵。
Objective To explore the effect of PI3 K signaling pathway activation on reproductive endocrine indexes in polycystic ovary syndrome(PCOS) rats. Methods Female SD rats were randomly divided into a control group, a model group and an intervention group(n =10, respectively). PCOS rat models were established by dehydroepiandrosterone(DHEA) except the control group. After successful modeling, the intervention group was subcutaneously injected with liraglutide on the back and neck of rats, while the model group and the control group were given the same dose of saline. After 10 hours of intervention, the ovarian histomorphological changes were observed, and the serum progesterone(P), testosterone(T), fasting plasma glucose(FPG), PI3 K mRNA expression level, AKT protein and phosphorylated protein kinase B(p-AKT) activity were measured. Results The ovarian structure of the model group was disordered, and there were many cystic dilated follicles near the capsule. Some of the follicles had no oocyte, and the radiation corona disappeared. The number of granulosa cell layers decreased and corpus luteum was rare. The granulosa cell layers of the intervention group were more than that of the model group, and the theca cell layers became thinner, mature follicles were seen, and the number of corpus luteum was more than that of the model group. There was no significant difference in serum P and FPG levels between the control group and the intervention group, but significant difference from those of the model group. The order of serum T levels in the three groups was: the control group < the intervention group < the model group(P < 0.05). The expression levels of PI3 K mRNA, AKT protein and p-AKT protein in the model group were lower than those in other two groups(P < 0.05); the expression levels of PI3 K protein in the intervention group were higher than those in the control group(P < 0.05), while the expression levels of AKT protein and p-AKT protein were similar to those in the control group(P > 0.05). Conclusion Liraglutide can inhibit androgen expression, increase progesterone levels, regulate glucose metabolism and promote ovulation by activating PI3 K signaling pathway in PCOS rats.
Objective To explore the effect of PI3 K signaling pathway activation on reproductive endocrine indexes in polycystic ovary syndrome(PCOS) rats. Methods Female SD rats were randomly divided into a control group, a model group and an intervention group(n =10, respectively). PCOS rat models were established by dehydroepiandrosterone(DHEA) except the control group. After successful modeling, the intervention group was subcutaneously injected with liraglutide on the back and neck of rats, while the model group and the control group were given the same dose of saline. After 10 hours of intervention, the ovarian histomorphological changes were observed, and the serum progesterone(P), testosterone(T), fasting plasma glucose(FPG), PI3 K mRNA expression level, AKT protein and phosphorylated protein kinase B(p-AKT) activity were measured. Results The ovarian structure of the model group was disordered, and there were many cystic dilated follicles near the capsule. Some of the follicles had no oocyte, and the radiation corona disappeared. The number of granulosa cell layers decreased and corpus luteum was rare. The granulosa cell layers of the intervention group were more than that of the model group, and the theca cell layers became thinner, mature follicles were seen, and the number of corpus luteum was more than that of the model group. There was no significant difference in serum P and FPG levels between the control group and the intervention group, but significant difference from those of the model group. The order of serum T levels in the three groups was: the control group < the intervention group < the model group(P < 0.05). The expression levels of PI3 K mRNA, AKT protein and p-AKT protein in the model group were lower than those in other two groups(P < 0.05); the expression levels of PI3 K protein in the intervention group were higher than those in the control group(P < 0.05), while the expression levels of AKT protein and p-AKT protein were similar to those in the control group(P > 0.05). Conclusion Liraglutide can inhibit androgen expression, increase progesterone levels, regulate glucose metabolism and promote ovulation by activating PI3 K signaling pathway in PCOS rats.
引文
[1]匡洪影,马珂昕,李威,等.隐丹参酮调节PCOS模型大鼠卵巢颗粒细胞生殖内分泌机能的机制研究[J].中医药学报,2017,45(5):40-44.
[2]Li T,Mo H,Chen W,et al.Role of the PI3K-Akt signaling pathway in the pathogenesis of polycystic ovary syndrome[J].Reproductive Sciences,2016,24(5):646-655.
[3]马文聪,刘建新,陈东思,等.PCOS病人胰岛素抵抗两条主要信号通路机制的研究进展[J].青岛大学医学院学报,2015,51(6):745-747.
[4]朱亮,邢福祺,全松,等.DHEA诱导SD大鼠PCOS模型LHR、INSR、AR基因甲基化的研究[J].中华生殖与避孕杂志,2010,30(1):9-14.
[5]李明明,潘文,康开彪,等.不同造模方法对大鼠多囊卵巢综合征伴胰岛素抵抗模型的影响[J].西部中医药,2015,28(4):11-14.
[6]李甜甜,张江宇,李荔,等.PI3K/Akt在多囊卵巢综合征发病机制中作用的研究进展[J].基础医学与临床,2016,36(11):1596-1602.
[7]马文聪,刘建新,祁秀娟,等.P38蛋白激酶抑制剂SB203580对多囊卵巢综合征卵巢颗粒细胞PI3K通路的影响[J].现代妇产科进展,2016,25(4):285-287.
[8]马欣,王蕊.胰岛素通过PI3K/AKT/GSK3通路促多囊卵巢综合征患者子宫内膜病变机制的研究[J].标记免疫分析与临床,2015,22(4):330-334.
[9]陈彬,张星光,李艳玲,等.利拉鲁肽与西格列汀分别联合二甲双胍治疗2型糖尿病效果观察[J].解放军医药杂志,2014,26(9):44-46.
[10]张星,魏琦,温维琴,等.利拉鲁肽对2型糖尿病合并肥胖患者血清趋化素和胰岛素抵抗的影响[J].检验医学与临床,2017,14(6):800-802.
[2]Li T,Mo H,Chen W,et al.Role of the PI3K-Akt signaling pathway in the pathogenesis of polycystic ovary syndrome[J].Reproductive Sciences,2016,24(5):646-655.
[3]马文聪,刘建新,陈东思,等.PCOS病人胰岛素抵抗两条主要信号通路机制的研究进展[J].青岛大学医学院学报,2015,51(6):745-747.
[4]朱亮,邢福祺,全松,等.DHEA诱导SD大鼠PCOS模型LHR、INSR、AR基因甲基化的研究[J].中华生殖与避孕杂志,2010,30(1):9-14.
[5]李明明,潘文,康开彪,等.不同造模方法对大鼠多囊卵巢综合征伴胰岛素抵抗模型的影响[J].西部中医药,2015,28(4):11-14.
[6]李甜甜,张江宇,李荔,等.PI3K/Akt在多囊卵巢综合征发病机制中作用的研究进展[J].基础医学与临床,2016,36(11):1596-1602.
[7]马文聪,刘建新,祁秀娟,等.P38蛋白激酶抑制剂SB203580对多囊卵巢综合征卵巢颗粒细胞PI3K通路的影响[J].现代妇产科进展,2016,25(4):285-287.
[8]马欣,王蕊.胰岛素通过PI3K/AKT/GSK3通路促多囊卵巢综合征患者子宫内膜病变机制的研究[J].标记免疫分析与临床,2015,22(4):330-334.
[9]陈彬,张星光,李艳玲,等.利拉鲁肽与西格列汀分别联合二甲双胍治疗2型糖尿病效果观察[J].解放军医药杂志,2014,26(9):44-46.
[10]张星,魏琦,温维琴,等.利拉鲁肽对2型糖尿病合并肥胖患者血清趋化素和胰岛素抵抗的影响[J].检验医学与临床,2017,14(6):800-802.