Xu Ge, Zhang Andong, Liu Jiandang, Wang Xi, Feng Jiwei, Chen Yuelai
Shanghai University of Chinese Traditional Medicine, Shanghai 201203, China.
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Chinese Medicine, Shanghai 200437, China.
Evid Based Complement Alternat Med. 2020 Jul 14;2020:3608062. doi: 10.1155/2020/3608062. eCollection 2020.
Polycystic ovarian syndrome (PCOS) occurs in women of reproductive age and is often characterized by reproductive and endocrine dysfunction. Androgens play a major role in PCOS, and previous studies reported abnormal expression of Connexin 43 (Cx43) in animal models of PCOS, suggesting an association of Cx43 with PCOS pathogenesis. Experimental and clinical evidence indicated that acupuncture may be a safe and effective approach for treating reproductive and endocrine disorders in women with PCOS. This study aimed to determine the effects of electroacupuncture (EA) on PCOS and its relationship with the expression of the androgen receptor (AR) and Cx43.
In total, 30 female Sprague Dawley rats (6 weeks old) were randomly divided into three groups: control group, letrozole (LE) group, and LE + EA group. Rats were administered LE solution (1.0 mg/kg) for 21 consecutive days to induce PCOS. For the LE + EA group, additional EA treatment was conducted (2 Hz, 20 min/d) with "Guanyuan" (CV3) for 14 consecutive days. After hematoxylin-eosin staining, the ovarian structure was observed with an optical microscope, and serum levels of the following hormones were examined via enzyme-linked immunosorbent assay (ELISA): testosterone (T), estradiol (E), sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH); luteinizing hormone (LH), insulin (INS), anti-Müllerian hormone (AMH), and inhibin B (INHB). Fasting blood glucose (FBG) levels were evaluated using glucose oxidase-peroxidase. Ovarian mRNA and protein expressions of AR and Cx43 were determined by real-time RT-PCR and Western blot analysis.
EA was found to restore the cyclicity and ovarian morphology in the PCOS rat model. Serum derived from the LE + EA group showed significant decreases in the levels of T, free androgen index (FAI), LH, LH/FSH ratio, AMH, INHB, and fasting serum insulin (FINS), and significant increases in the levels of E, FSH, and SHBG. Western blot analysis showed a decreased protein expression of ovarian AR and Cx43; real-time RT-PCR showed reduced expression of ovarian mRNA levels of AR and Cx43.
In conclusion, our results showed that EA can ease hyperandrogenism and polycystic ovary morphology in PCOS rats. Furthermore, EA counteracted the letrozole-induced upregulation of AR and Cx43. These results suggested that acupuncture can break the vicious cycle initiated by excessive androgen secretion and may be an effective treatment method for improving the reproductive and endocrine dysfunction caused by PCOS.
多囊卵巢综合征（PCOS）发生于育龄女性，常以生殖和内分泌功能障碍为特征。雄激素在PCOS中起主要作用，既往研究报道在PCOS动物模型中连接蛋白43（Cx43）表达异常，提示Cx43与PCOS发病机制有关。实验和临床证据表明，针刺可能是治疗PCOS女性生殖和内分泌紊乱的一种安全有效的方法。本研究旨在确定电针（EA）对PCOS的影响及其与雄激素受体（AR）和Cx43表达的关系。
总共30只6周龄雌性Sprague Dawley大鼠随机分为三组：对照组、来曲唑（LE）组和LE + EA组。连续21天给大鼠腹腔注射LE溶液（1.0 mg/kg）以诱导PCOS。对于LE + EA组，额外进行EA治疗（2 Hz，20分钟/天），针刺“关元”（CV3），连续14天。苏木精-伊红染色后，用光学显微镜观察卵巢结构，并通过酶联免疫吸附测定（ELISA）检测以下激素的血清水平：睾酮（T）、雌二醇（E）、性激素结合球蛋白（SHBG）、促卵泡激素（FSH）；促黄体生成素（LH）、胰岛素（INS）、抗苗勒管激素（AMH）和抑制素B（INHB）。使用葡萄糖氧化酶-过氧化物酶评估空腹血糖（FBG）水平。通过实时RT-PCR和蛋白质印迹分析测定卵巢中AR和Cx43的mRNA和蛋白质表达。
发现EA可恢复PCOS大鼠模型的月经周期和卵巢形态。LE + EA组血清中T、游离雄激素指数（FAI）、LH、LH/FSH比值、AMH、INHB和空腹血清胰岛素（FINS）水平显著降低，E、FSH和SHBG水平显著升高。蛋白质印迹分析显示卵巢AR和Cx43的蛋白表达降低；实时RT-PCR显示卵巢中AR和Cx43的mRNA水平表达降低。
总之，我们的结果表明EA可缓解PCOS大鼠的高雄激素血症和多囊卵巢形态。此外，EA可抵消来曲唑诱导的AR和Cx43上调。这些结果提示针刺可打破由雄激素分泌过多引发的恶性循环，可能是改善PCOS所致生殖和内分泌功能障碍的有效治疗方法。
