目的:探讨irisin对多囊卵巢综合征(PCOS)患者卵巢胰岛素抵抗(IR)的影响及其可能的作用途径。
方法:我们使用PoretskyL\'s方法建立了PCOS模型,然后将PCOS大鼠随机分为模型组(M)和艾瑞辛组(I),正常大鼠(N)作为对照。然后对I组大鼠注射重组irisin。然后循环空腹血糖(FBG)的水平,空腹胰岛素(FINS),观察各组IR(HOMA-IR)、PI3K/AKT和MAPK/ERK通路的稳态模型评估,以及irisin对PCOS大鼠卵巢循环HOMA-IR和PI3K/AKT和MAPK/ERK通路的影响。
结果:与正常组相比,FBG的水平,FINS,模型组HOMA-IR明显升高(p<0.001,p<0.001,p<0.001),p-PI3K的IHC平均光密度水平,PI3K,p-AKT,和AKT(分别为p=0.015,p=0.010,p=0.005和p=0.009)以及PI3K和AKT的mRNA浓度(分别为p=0.001和p=0.005)降低,而p-ERK的平均光密度水平,ERK(分别为p=0.011和p=0.013)和ERK的mRNA浓度(p<0.001)在卵巢中增加。在艾瑞辛干预之后,与模型组相比,FBG的水平,FINS,irisin组大鼠HOMA-IR显著降低(p=0.001,p<0.001,p<0.001),p-PI3K的IHC平均光密度水平,PI3K,p-AKT,和AKT(分别为p=0.030,p=0.024,p=0.012和p=0.025)以及PI3K和AKT的mRNA浓度(分别为p=0.002和p=0.003)显着增加,而p-ERK的平均光密度水平,ERK(分别为p=0.004和p=0.026)和ERK的mRNA浓度(p=0.001)显着降低。
结论:我们的研究表明,irisin不仅可以改善循环胰岛素抵抗,但也可能通过增加PI3K/AKT信号的活性和减少MAPK/ERK信号的活性来改善卵巢IR。
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.
CONCLUSIONS: 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.