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鸢尾素对多囊卵巢综合征大鼠卵巢磷脂酰肌醇-3-激酶/蛋白激酶 B 信号通路和丝裂原活化蛋白激酶/细胞外信号调节激酶通路的影响。

Effect of irisin on ovarian phosphatidylinositol-3-kinase/protein kinase B signaling pathway and mitogen-activated protein kinase/extracellular signal-regulated kinase pathways of rats with polycystic ovary syndrome.

机构信息

The First Affiliated Hospital of Xingtai Medical College, Xingtai, Hebei, People's Republic of China.

Department of Traditional Chinese Medicine, Xingtai Medical College, Xingtai, Hebei, People's Republic of China.

出版信息

J Obstet Gynaecol Res. 2024 Oct;50(10):1945-1951. doi: 10.1111/jog.16076. Epub 2024 Sep 3.

DOI:10.1111/jog.16076
PMID:39225708
Abstract

OBJECTIVE

To investigate the independent effects of irisin on insulin resistance (IR) in ovary of polycystic ovary syndrome (PCOS) and explore possible pathways.

METHODS

We established PCOS medel using Poretsky L's method, then PCOS rats were randomly divided into model group (M) and irisin group (I), and normal rats (N) were used as the control. Then rats in the group I were injected with recombinant irisin. Then the levels of circulating fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of IR (HOMA-IR) and PI3K/AKT and MAPK/ERK pathways in each group were observed, as well as the effects of irisin on the levels of circulating HOMA-IR and PI3K/AKT and MAPK/ERK pathways in ovary of PCOS rats were evaluated.

RESULTS

Compared with normal group, levels of FBG, FINS, and HOMA-IR of model group were significantly increased (p < 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.015, p = 0.010, p = 0.005, and p = 0.009, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.001, and p = 0.005, respectively) were decreased, while the levels of average optical density of p-ERK, ERK (p = 0.011, and p = 0.013, respectively) and level of mRNA concentration of ERK (p < 0.001) were increased in ovary. After irisin intervention, compared with model group, levels of FBG, FINS, and HOMA-IR of rats in irisin group were significantly decreased (p = 0.001, p < 0.001, and p < 0.001, respectively), levels of average optical density by IHC of p-PI3K, PI3K, p-AKT, and AKT (p = 0.030, p = 0.024, p = 0.012, and p = 0.025, respectively) and levels of mRNA concentration of PI3K and AKT (p = 0.002, and p = 0.003, respectively) were significantly increased, while the levels of average optical density of p-ERK, ERK (p = 0.004, and p = 0.026, respectively) and level of mRNA concentration of ERK (p = 0.001) were significantly decreased.

CONCLUSION

Our study demonstrated that irisin could not only improve circulating insulin resistance, but may also improve ovarian IR through an increase in the activity of PI3K/AKT signaling and a decrease of MAPK/ERK signaling.

摘要

目的

探讨鸢尾素对多囊卵巢综合征(PCOS)卵巢胰岛素抵抗(IR)的独立影响,并探讨可能的途径。

方法

采用 Poretsky L 法建立 PCOS 模型,然后将 PCOS 大鼠随机分为模型组(M)和鸢尾素组(I),并以正常大鼠(N)作为对照。然后,给 I 组大鼠注射重组鸢尾素。观察各组大鼠的空腹血糖(FBG)、空腹胰岛素(FINS)、胰岛素抵抗指数(HOMA-IR)、PI3K/AKT 和 MAPK/ERK 通路水平,以及鸢尾素对 PCOS 大鼠卵巢循环 HOMA-IR 和 PI3K/AKT 和 MAPK/ERK 通路水平的影响。

结果

与正常组相比,模型组的 FBG、FINS 和 HOMA-IR 水平明显升高(p<0.001、p<0.001 和 p<0.001),PI3K/AKT 和 MAPK/ERK 通路的平均光密度 IHC 水平(p=0.015、p=0.010、p=0.005 和 p=0.009)以及 PI3K 和 AKT 的 mRNA 浓度(p=0.001 和 p=0.005)均降低,而卵巢中 p-ERK、ERK 的平均光密度(p=0.011 和 p=0.013)和 ERK 的 mRNA 浓度(p<0.001)水平升高。鸢尾素干预后,与模型组相比,鸢尾素组大鼠的 FBG、FINS 和 HOMA-IR 水平明显降低(p=0.001、p<0.001 和 p<0.001),PI3K/AKT 和 MAPK/ERK 通路的平均光密度 IHC 水平(p=0.030、p=0.024、p=0.012 和 p=0.025)以及 PI3K 和 AKT 的 mRNA 浓度(p=0.002 和 p=0.003)均升高,而 p-ERK、ERK 的平均光密度(p=0.004 和 p=0.026)和 ERK 的 mRNA 浓度(p=0.001)水平明显降低。

结论

本研究表明,鸢尾素不仅可以改善循环胰岛素抵抗,还可以通过增加 PI3K/AKT 信号的活性和降低 MAPK/ERK 信号来改善卵巢 IR。

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