ABSTRACT Polycystic ovary syndrome (PCOS) is recognized as a general endocrine disease and reproductive disorder. Although evidence indicates that PCOS has a complex etiology and genetic basis, the pathogenic mechanisms and signal pathway in PCOS remain unclear. In this study, the normal structure of follicle and corpus luteum were observed, and no cyst nor hyperemia was observed under the light microscopic study with hematoxylin and eosin (H&E) staining. Eestosterone and progesterone were evaluated by radioimmunoassay in rat serum. The alterations of proliferative ability and cell cycle distribution of each group were assessed by Cell Counting Kit-8 (CCK8) assay and flow cytometry. The protein expression of p-mTOR/mTOR, p-PI3K/PI3K, p-AKT/AKT, and GAPDH were analyzed by western blotting. Both doses of PLB could benefit the ovarian morphology and polycystic property. PLBinduced a suppress effect on the proliferation of rat ovarian granulosa cells. In addition, PLB also induced concentration-dependent apoptosis in rat ovarian granulosa cells. The rat ovarian granulosa cells treated with PLB that the expression levels of p-AKT, p-mTOR, and p-PI3K were significantly decreased in a concentration-dependent manner. PLB not only plays a critical role in attenuating the pathology and polycystic property changes in the ovary but can also induce rat ovarian granulosa cell apoptosis through the PI3K/Akt/mTOR signal pathway. This study showed the innovative role of PLB in the pathogenesis of PCOS and provides a new therapeutic modality for the treatment of PCOS.

中文翻译：

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Plumbagin通过灭活PI3K/Akt/mTOR通路抑制多囊卵巢综合征卵巢颗粒细胞增殖促进凋亡

摘要 多囊卵巢综合征（PCOS）被认为是一种全身内分泌疾病和生殖系统疾病。尽管有证据表明 PCOS 具有复杂的病因和遗传基础，但 PCOS 的发病机制和信号通路仍不清楚。本次研究中，卵泡和黄体结构正常，苏木精伊红（H&E）染色光镜下未见囊肿和充血。通过放射免疫测定法在大鼠血清中评估雌酮和孕酮。通过Cell Counting Kit-8（CCK8）检测和流式细胞术评估各组增殖能力和细胞周期分布的变化。通过蛋白质印迹分析 p-mTOR/mTOR、p-PI3K/PI3K、p-AKT/AKT 和 GAPDH 的蛋白质表达。两种剂量的 PLB 均可有益于卵巢形态和多囊性。PLB对大鼠卵巢颗粒细胞增殖有抑制作用。此外，PLB 还诱导大鼠卵巢颗粒细胞浓度依赖性凋亡。用PLB处理的大鼠卵巢颗粒细胞p-AKT、p-mTOR和p-PI3K的表达水平以浓度依赖性方式显着降低。PLB 不仅在减轻卵巢病理和多囊性改变方面起着关键作用，而且还可以通过 PI3K/Akt/mTOR 信号通路诱导大鼠卵巢颗粒细胞凋亡。本研究显示了PLB在PCOS发病机制中的创新作用，为PCOS的治疗提供了一种新的治疗方式。PLB对大鼠卵巢颗粒细胞增殖有抑制作用。此外，PLB 还诱导大鼠卵巢颗粒细胞浓度依赖性凋亡。用PLB处理的大鼠卵巢颗粒细胞p-AKT、p-mTOR和p-PI3K的表达水平以浓度依赖性方式显着降低。PLB 不仅在减轻卵巢病理和多囊性改变方面起着关键作用，而且还可以通过 PI3K/Akt/mTOR 信号通路诱导大鼠卵巢颗粒细胞凋亡。本研究显示了PLB在PCOS发病机制中的创新作用，为PCOS的治疗提供了一种新的治疗方式。PLB对大鼠卵巢颗粒细胞增殖有抑制作用。此外，PLB 还诱导大鼠卵巢颗粒细胞浓度依赖性凋亡。用PLB处理的大鼠卵巢颗粒细胞p-AKT、p-mTOR和p-PI3K的表达水平以浓度依赖性方式显着降低。PLB 不仅在减轻卵巢病理和多囊性改变方面起着关键作用，而且还可以通过 PI3K/Akt/mTOR 信号通路诱导大鼠卵巢颗粒细胞凋亡。本研究显示了PLB在PCOS发病机制中的创新作用，为PCOS的治疗提供了一种新的治疗方式。用PLB处理的大鼠卵巢颗粒细胞p-AKT、p-mTOR和p-PI3K的表达水平以浓度依赖性方式显着降低。PLB 不仅在减轻卵巢病理和多囊性改变方面起着关键作用，而且还可以通过 PI3K/Akt/mTOR 信号通路诱导大鼠卵巢颗粒细胞凋亡。本研究显示了PLB在PCOS发病机制中的创新作用，为PCOS的治疗提供了一种新的治疗方式。用PLB处理的大鼠卵巢颗粒细胞p-AKT、p-mTOR和p-PI3K的表达水平以浓度依赖性方式显着降低。PLB 不仅在减轻卵巢病理和多囊性改变方面起着关键作用，而且还可以通过 PI3K/Akt/mTOR 信号通路诱导大鼠卵巢颗粒细胞凋亡。本研究显示了PLB在PCOS发病机制中的创新作用，为PCOS的治疗提供了一种新的治疗方式。