Acupuncture, a therapy of traditional Chinese medicine, is confirmed to exert the therapeutic action on polycystic ovary syndrome (PCOS). However, the detailed therapeutic mechanisms of acupuncture in PCOS remain ambiguous. In this study, we further investigated whether electroacupuncture (EA) alleviated PCOS-like symptoms in rats via regulating a metabolic regulator, sterol regulatory element binding protein-1 (SREBP1). The PCOS-like rat model was built by hypodermic injection with dehydroepiandrosterone (DHEA). The rats were subjected to EA intervention (ST29 and SP6 acupuncture points) for 5 weeks. Primary granulosa cells were isolated from control and PCOS-like rats for evaluating insulin resistance, mitochondrial dysfunction and oxidative stress in vitro. The expression of SREBP1 was increased in PCOS-like rats, which was suppressed by EA treatment. In addition, lentivirus-mediated overexpression of SREBP1 restrained EA treatment-induced improvement in pathological changes, serum hormone levels and insulin resistance in rats. In addition, overexpression of SREBP1 repressed insulin-stimulated phosphorylation of insulin receptor β (IR) and AKT in primary granulosa cells. Moreover, upregulation of SREBP1 further exacerbated mitochondrial dysfunction and oxidative stress in granulosa cells isolated from PCOS-like rats. Mechanically, EA treatment suppressed SREBP1 expression through inducing the activation of AMP-activated protein kinase (AMPK) signaling pathway in PCOS-like rats. EA intervention alleviated PCOS-like symptoms in rats via improving IR, mitochondrial dysfunction and oxidative stress through regulating SREBP1, a lipid metabolism regulator. Our findings illuminate the novel protective mechanisms of EA in the treatment of PCOS.

中文翻译：

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电针抗大鼠多囊卵巢样综合征效应的新机制：抑制SREBP1以减轻胰岛素抵抗，线粒体功能障碍和氧化应激

针灸是中药治疗方法，已证实对多囊卵巢综合征（PCOS）具有治疗作用。但是，针灸治疗PCOS的详细治疗机制仍不明确。在这项研究中，我们进一步研究了电针（EA）是否通过调节代谢调节剂，固醇调节元件结合蛋白1（SREBP1）减轻了大鼠PCOS样症状。通过皮下注射脱氢表雄酮（DHEA）建立PCOS样大鼠模型。大鼠接受EA干预（ST29和SP6穴位）5周。从对照组和PCOS样大鼠中分离出原代颗粒细胞，以在体外评估胰岛素抵抗，线粒体功能障碍和氧化应激。在PCOS样大鼠中SREBP1的表达增加，被电针治疗抑制了。此外，慢病毒介导的SREBP1的过表达抑制了EA治疗诱导的大鼠病理变化，血清激素水平和胰岛素抵抗的改善。此外，SREBP1的过表达抑制了原代颗粒细胞中胰岛素刺激的胰岛素受体β（IR）和AKT的磷酸化。此外，SREBP1的上调进一步加重了从PCOS样大鼠分离出的颗粒细胞中的线粒体功能障碍和氧化应激。在机械上，EA处理通过诱导PCOS样大鼠中AMP激活的蛋白激酶（AMPK）信号通路的激活来抑制SREBP1表达。EA干预通过调节脂质代谢调节剂SREBP1改善IR，线粒体功能障碍和氧化应激，从而减轻了大鼠PCOS样症状。