Maliqueo Manuel, Benrick Anna, Marcondes Rodrigo Rodrigues, Johansson Julia, Sun Miao, Stener-Victorin Elisabet
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Laboratorio de Endocrinología y Metabolismo, Departamento de Medicina Occidente, Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Exp Physiol. 2017 Jan 1;102(1):113-127. doi: 10.1113/EP085983.
What is the central question of this study? The effectiveness of low-frequency electroacupuncture in the treatment of metabolic disorders associated with polycystic ovary syndrome (PCOS), an endocrine-metabolic disorder characterized by an imbalance in sex steroid production, is controversial. What is the main finding and its importance? In a rat model of PCOS induced by the inhibition of P450 aromatase, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol but did not improve the insulin resistance or the adipose tissue dysfunction, suggesting that a balance of sex steroids is needed to restore the metabolic function in this rat model of PCOS. Low-frequency electroacupuncture restores sex steroid synthesis and sympathetic activity in women with polycystic ovary syndrome, which may ameliorate its metabolic disturbances, probably by modulating sympathetic nerve activity or sex steroid synthesis. We investigated whether low-frequency electroacupuncture regulates the metabolic function to the same extent as treatment with estradiol or β-adrenergic blocking in a rat model of polycystic ovary syndrome induced by a P450 aromatase inhibitor (letrozole). Letrozole (200 μg day ) or placebo pellets were implanted in prepubertal Wistar rats. Six weeks thereafter, rats were treated for 5-6 weeks with the following: low-frequency electroacupuncture (5 days per week); a β-adrenergic blocker (propranolol hydrochloride, 0.1 mg kg , 5 days per week); or 17β-estradiol (2.0 μg) every fourth day. Body weight development, body composition, locomotor activity, insulin sensitivity, tissue-specific glucose uptake, lipid profile, adipocyte size, serum concentrations of adiponectin and insulin, and gene expression in inguinal fat were measured. All treatments increased circulating levels of low-density lipoprotein-cholesterol. Estradiol treatment restored locomotor activity and increased insulin sensitivity but did not modify the glucose uptake in muscle and fat. An upregulation of genes related to insulin sensitivity and downregulation of genes related to adipogenesis were observed in subcutaneous adipose tissue from rats exposed to letrozole. Only estradiol treatment normalized the expression of these genes. In conclusion, low-frequency electroacupuncture increased low-density lipoprotein-cholesterol without affecting insulin sensitivity or adipose tissue function, which could suggest effects on hepatic lipid regulation, probably mediated by the action of estradiol or the β-adrenergic pathway.
本研究的核心问题是什么？低频电针治疗与多囊卵巢综合征（PCOS）相关的代谢紊乱的有效性存在争议，PCOS是一种以内分泌代谢紊乱为特征的疾病，其特点是性类固醇生成失衡。主要发现及其重要性是什么？在通过抑制P450芳香化酶诱导的PCOS大鼠模型中，低频电针增加了低密度脂蛋白胆固醇，但并未改善胰岛素抵抗或脂肪组织功能障碍，这表明在该PCOS大鼠模型中需要性类固醇的平衡来恢复代谢功能。低频电针可恢复多囊卵巢综合征女性的性类固醇合成和交感神经活动，这可能通过调节交感神经活动或性类固醇合成来改善其代谢紊乱。我们研究了在由P450芳香化酶抑制剂（来曲唑）诱导的多囊卵巢综合征大鼠模型中，低频电针调节代谢功能的程度是否与雌二醇治疗或β-肾上腺素能阻断治疗相同。将来曲唑（200μg/天）或安慰剂药丸植入青春期前的Wistar大鼠体内。六周后，对大鼠进行以下治疗5-6周：低频电针（每周5天）；β-肾上腺素能阻滞剂（盐酸普萘洛尔，0.1mg/kg，每周5天）；或每四天注射17β-雌二醇（2.0μg）。测量体重发育、身体组成、运动活动、胰岛素敏感性、组织特异性葡萄糖摄取、血脂谱、脂肪细胞大小、脂联素和胰岛素的血清浓度以及腹股沟脂肪中的基因表达。所有治疗均增加了循环中的低密度脂蛋白胆固醇水平。雌二醇治疗恢复了运动活动并提高了胰岛素敏感性，但未改变肌肉和脂肪中的葡萄糖摄取。在暴露于来曲唑的大鼠的皮下脂肪组织中，观察到与胰岛素敏感性相关的基因上调以及与脂肪生成相关的基因下调。只有雌二醇治疗使这些基因的表达正常化。总之，低频电针增加了低密度脂蛋白胆固醇，而不影响胰岛素敏感性或脂肪组织功能，这可能表明其对肝脏脂质调节有影响，可能是由雌二醇或β-肾上腺素能途径的作用介导的。
