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针刺通过 LncMEG3 抑制 PI3K/AKT/mTOR 通路调节多囊卵巢综合征排卵障碍患者卵巢颗粒细胞自噬。

Acupuncture regulates the autophagy of ovarian granulosa cells in polycystic ovarian syndrome ovulation disorder by inhibiting the PI3K/AKT/mTOR pathway through LncMEG3.

机构信息

Guangxi University of Chinese Medicine, Nanning, Guangxi 530200, China.

Fangchenggang Hospital Affiliated to Guangxi University of Chinese Medicine, Fangchenggang, Guangxi 538000, China.

出版信息

Biomed Pharmacother. 2021 Dec;144:112288. doi: 10.1016/j.biopha.2021.112288. Epub 2021 Oct 13.

Abstract

The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulation dysfunction, which are caused by the excessive autophagy of ovarian granulosa cells. Acupuncture has been shown to improve ovulation dysfunction and abnormal follicular development in PCOS patients, but its mechanism is unclear. This study hypothesized that the beneficial effects of acupuncture are the result of LncMEG3-mediated effects on the PI3K/AKT/mTOR pathway. Acupuncture (CV-4, RN-3, CV-6, SP-6 and EX-CA 1) was used to treat a rat model of polycystic ovary syndrome. Hematoxylin-eosin staining was used to observe ovarian morphology and enzyme-linked immunosorbent assay, western blotting, immunohistochemistry and real-time PCR were used to detect LH, E2, FSH, T, AMH, LncMEG3, PI3K, AKT, mTOR, P62 and LC3II/I expression. The ovarian morphology of 90% of the rats in the acupuncture treatment group was significantly improved after 11 consecutive days of therapy. Acupuncture also resulted in a significant decrease in serum LH, FSH, T and AMH levels and a significant increase in E2 level (P<0.01). LncMEG3, PI3K, AKT, mTOR, P62 and LC3II/I expression was decreased in ovarian granulosa cells after acupuncture compared with PCOS and lentiviral Intervention Group (P<0.05), while the expression of follicle stimulating hormone receptor was increased (P<0.05). These results indicate that acupuncture can down-regulate the expression of LncMEG3 and thereby inhibit the PI3K/AKT/mTOR pathway, reducing granulosa cell autophagy and normalizing their proliferation. These factors ultimately remedy abnormal follicular development. These findings suggest that acupuncture has clinical potential as a safe treatment for PCOS ovulatory dysfunction.

摘要

多囊卵巢综合征(PCOS)的主要特征是卵泡发育异常和排卵功能障碍,这是由卵巢颗粒细胞过度自噬引起的。针刺已被证明可以改善 PCOS 患者的排卵功能障碍和异常卵泡发育,但机制尚不清楚。本研究假设针刺的有益作用是 LncMEG3 对 PI3K/AKT/mTOR 通路的影响所致。采用针刺(CV-4、RN-3、CV-6、SP-6 和 EX-CA 1)治疗多囊卵巢综合征大鼠模型。苏木精-伊红染色观察卵巢形态,酶联免疫吸附试验、western blot、免疫组化和实时 PCR 检测 LH、E2、FSH、T、AMH、LncMEG3、PI3K、AKT、mTOR、P62 和 LC3II/I 的表达。针刺治疗组 90%的大鼠卵巢形态在连续 11 天治疗后明显改善。针刺还导致血清 LH、FSH、T 和 AMH 水平显著降低,E2 水平显著升高(P<0.01)。与 PCOS 和慢病毒干预组相比,针刺后卵巢颗粒细胞中 LncMEG3、PI3K、AKT、mTOR、P62 和 LC3II/I 的表达降低(P<0.05),而卵泡刺激素受体的表达增加(P<0.05)。这些结果表明,针刺可以下调 LncMEG3 的表达,从而抑制 PI3K/AKT/mTOR 通路,减少颗粒细胞自噬并使其增殖正常化。这些因素最终纠正了异常的卵泡发育。这些发现表明,针刺作为一种安全的治疗多囊卵巢综合征排卵功能障碍的方法具有临床潜力。

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