针刺通过 LncMEG3 介导的 miR-21-3p 抑制调节多囊卵巢综合征相关异常卵泡发育中的卵巢颗粒细胞凋亡。

BACKGROUND: The main features of polycystic ovary syndrome (PCOS) are abnormal follicular development and ovulatory dysfunction, which are caused by excessive apoptosis of ovarian granulosa cells. Acupuncture has been shown to improve follicular development abnormalities in patients with PCOS, but its mechanism is unknown. This study hypothesized that the mechanism of acupuncture on follicular development abnormalities in PCOS patients is the inhibition of granulosa cell apoptosis through LncMEG3-mediated regulation of miR-21-3p. METHODS: A PCOS-like rat model was established using subcutaneous injection of dehydroepiandrosterone (DHEA). Acupuncture was performed on rats for 15 d (CV-4, RN-3, CV-6, SP-6 and EX-CA 1). Ovarian morphology was observed by HE staining, and sex hormone and AMH levels were detected by ELISA. Primary granulosa cells were isolated from each group of rats to assess the association of acupuncture treatment, LncMEG3, miR-21-3p, and granulosa cell apoptosis in rats with PCOS. RESULTS: LncMEG3 and miR-21-3p were highly expressed in the ovarian granulosa cells of rats with PCOS, and LncMEG3-mediated regulation of miR-21-3p was involved in the development of PCOS in rats. Silencing of MEG3 attenuated sex hormone dysregulation and ovarian histopathological changes in PCOS rats and promoted follicle cell development and maturation. In addition, silencing MEG3 increased the viability and number of granulosa cells. In addition, silencing MEG3 further inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats. Acupuncture improved polycystic ovarian morphology and sex hormone levels in PCOS rats. Acupuncture intervention increased the viability and number of granulosa cells. Acupuncture intervention inhibited early and late apoptosis of ovarian granulosa cells in PCOS rats by targeting miR-21-3p via LncMEG3. CONCLUSION: These results suggest that acupuncture can downregulate LncMEG3, thereby targeting and regulating miR-21-3p to suppress early and late granulosa cell apoptosis and normalize their proliferation. These factors ultimately compensate for abnormal follicular development. These findings shed light on the clinical potential of acupuncture as a safe treatment for follicular developmental abnormalities in PCOS.

背景：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凋亡引起的。针刺已被证明可以改善 PCOS 患者的卵泡发育异常，但具体机制尚不清楚。本研究假设针刺治疗 PCOS 患者卵泡发育异常的机制是通过 LncMEG3 介导的 miR-21-3p 调节来抑制颗粒细胞凋亡。

方法：采用皮下注射脱氢表雄酮（DHEA）建立 PCOS 样大鼠模型。对大鼠进行 15 天的针刺治疗（CV-4、RN-3、CV-6、SP-6 和 EX-CA 1）。通过 HE 染色观察卵巢形态，通过 ELISA 检测性激素和 AMH 水平。从各组大鼠中分离初级颗粒细胞，评估针刺治疗、LncMEG3、miR-21-3p 与 PCOS 大鼠颗粒细胞凋亡的相关性。

结果：PCOS 大鼠卵巢颗粒细胞中 LncMEG3 和 miR-21-3p 表达水平较高，LncMEG3 介导的 miR-21-3p 调节参与了 PCOS 大鼠的发病机制。MEG3 沉默可减轻 PCOS 大鼠的性激素失调和卵巢组织病理学改变，并促进卵泡细胞的发育和成熟。此外，沉默 MEG3 可增加颗粒细胞的活力和数量。此外，沉默 MEG3 可进一步抑制 PCOS 大鼠卵巢颗粒细胞的早期和晚期凋亡。针刺可改善 PCOS 大鼠多囊卵巢形态和性激素水平。针刺干预可通过 LncMEG3 靶向 miR-21-3p 增加颗粒细胞的活力和数量，抑制 PCOS 大鼠卵巢颗粒细胞的早期和晚期凋亡。

结论：这些结果表明，针刺可下调 LncMEG3，从而靶向和调节 miR-21-3p 抑制早期和晚期颗粒细胞凋亡并使其增殖正常化。这些因素最终补偿了异常的卵泡发育。这些发现为针刺作为治疗 PCOS 卵泡发育异常的安全治疗方法提供了临床依据。