Maliqueo Manuel, Benrick Anna, Alvi Asif, Johansson Julia, Sun Miao, Labrie Fernand, Ohlsson Claes, Stener-Victorin Elisabet
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden; Laboratorio de Endocrinología y Metabolismo, Departamento de Medicina Occidente, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Institute of Neuroscience and Physiology, Department of Physiology, Sahlgrenska Academy, University of Gothenburg, Sweden.
Mol Cell Endocrinol. 2015 Sep 5;412:159-69. doi: 10.1016/j.mce.2015.04.026. Epub 2015 May 8.
Acupuncture with combined manual and low-frequency electrical stimulation, or electroacupuncture (EA), reduces endocrine and reproductive dysfunction in women with polycystic ovary syndrome (PCOS), likely by modulating sympathetic nerve activity or sex steroid synthesis. To test this hypothesis, we induced PCOS in rats by prepubertal implantation of continuous-release letrozole pellets (200 µg/day) or vehicle. Six weeks later, rats were treated for 5-6 weeks with low-frequency EA 5 days/week, subcutaneous injection of 17β-estradiol (2.0 µg) every fourth day, or a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg/kg) 5 days/week. Letrozole controls were handled without needle insertion or injected with sesame oil every fourth day. Estrous cyclicity, ovarian morphology, sex steroids, gonadotropins, insulin-like growth factor I, bone mineral density, and gene and protein expression in ovarian tissue were measured. Low-frequency EA induced estrous-cycle changes, decreased high levels of circulating luteinizing hormone (LH) and the LH/follicle-stimulating hormone (FSH) ratio, decreased high ovarian gene expression of adiponectin receptor 2, and increased expression of adiponectin receptor 2 protein and phosphorylation of ERK1/2. EA also increased cortical bone mineral density. Propranolol decreased ovarian expression of Foxo3, Srd5a1, and Hif1a. Estradiol decreased circulating LH, induced estrous cycle changes, and decreased ovarian expression of Adipor1, Foxo3, and Pik3r1. Further, total bone mineral density was higher in the letrozole-estradiol group. Thus, EA modulates the circulating gonadotropin levels independently of sex steroids or β-adrenergic action and affects the expression of ovarian adiponectin system.
针刺结合手法和低频电刺激,即电针(EA),可减轻多囊卵巢综合征(PCOS)女性的内分泌和生殖功能障碍,可能是通过调节交感神经活动或性类固醇合成来实现的。为了验证这一假设,我们通过在青春期前植入持续释放来曲唑微丸(200μg/天)或赋形剂诱导大鼠患PCOS。六周后,大鼠每周接受5天的低频电针治疗5 - 6周,每四天皮下注射17β - 雌二醇(2.0μg),或每周接受5天的β - 肾上腺素能阻滞剂(盐酸普萘洛尔,0.1mg/kg)治疗。来曲唑对照组不进行针刺或每四天注射芝麻油。测量动情周期、卵巢形态、性类固醇、促性腺激素、胰岛素样生长因子I、骨矿物质密度以及卵巢组织中的基因和蛋白质表达。低频电针诱导动情周期变化,降低循环中高水平的黄体生成素(LH)和LH/卵泡刺激素(FSH)比值,降低卵巢中脂联素受体2的高基因表达,并增加脂联素受体2蛋白的表达和ERK1/2的磷酸化。电针还增加皮质骨矿物质密度。普萘洛尔降低卵巢中Foxo3、Srd5a1和Hif1a的表达。雌二醇降低循环中的LH,诱导动情周期变化,并降低卵巢中Adipor1、Foxo3和Pik3r1的表达。此外,来曲唑 - 雌二醇组的总骨矿物质密度更高。因此,电针独立于性类固醇或β - 肾上腺素能作用调节循环促性腺激素水平,并影响卵巢脂联素系统的表达。