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全身性脂联素治疗可逆转动物模型中的多囊卵巢综合征样特征。

Systemic adiponectin treatment reverses polycystic ovary syndrome-like features in an animal model.

作者信息

Singh Anusha, Bora Puran, Krishna Amitabh

机构信息

Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi 221005, India.

Jones Eye Institute, Pat and Willard Walker Eye Research Center, University of Arkansas for Medical Sciences, 4301 West Markham, Little Rock, AR 72205, USA.

出版信息

Reprod Fertil Dev. 2018 Mar;30(4):571-584. doi: 10.1071/RD17255.

Abstract

The present study examined the efficacy of adiponectin for regulating the reproductive, metabolic and fertility status of mice with polycystic ovary syndrome (PCOS). PCOS was induced in prepubertal (21- to 22-day-old) mice using dehydroepiandrosterone (6mg 100g-1day-1 for 25days), after which mice were administered either a low or high dose of adiponectin (5 or 15µgmL-1, s.c., respectively). PCOS mice exhibited typical features, including the presence of numerous cystic follicles, increased circulating androgens, increased body mass, altered steroidogenesis, decreased insulin receptor expression and increased serum triglycerides, serum glucose, Toll-like receptor (TLR)-4 (a marker of inflammation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis). These parameters were significantly correlated with a reduction in adiponectin in PCOS mice compared with vehicle-treated control mice. Exogenous adiponectin treatment of PCOS mice restored body mass and circulating androgen, triglyceride and glucose levels. Adiponectin also restored ovarian expression of steroidogenic markers (LH receptors, steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase), insulin receptor, TLR-4 and VEGF levels in control mice. Adiponectin restored ovulation in PCOS mice, as indicated by the presence of a corpus luteum and attainment of pregnancy. These findings suggest that adiponectin effectively facilitates fertility in anovulatory PCOS. We hypothesise that systemic adiponectin treatment may be a promising therapeutic strategy for the management of PCOS.

摘要

本研究检测了脂联素对调节多囊卵巢综合征(PCOS)小鼠生殖、代谢和生育状态的功效。使用脱氢表雄酮(6mg 100g-1天-1,持续25天)在青春期前(21至22日龄)小鼠中诱导PCOS,之后分别给小鼠皮下注射低剂量或高剂量的脂联素(分别为5或15µgmL-1)。PCOS小鼠表现出典型特征,包括存在大量囊性卵泡、循环雄激素增加、体重增加、类固醇生成改变、胰岛素受体表达降低以及血清甘油三酯、血糖、Toll样受体(TLR)-4(炎症标志物)和血管内皮生长因子(VEGF;血管生成标志物)增加。与用溶剂处理的对照小鼠相比,这些参数与PCOS小鼠脂联素减少显著相关。对PCOS小鼠进行外源性脂联素治疗可恢复体重以及循环雄激素、甘油三酯和血糖水平。脂联素还可恢复对照小鼠卵巢中类固醇生成标志物(促黄体生成素受体、类固醇生成急性调节蛋白和3β-羟基类固醇脱氢酶)、胰岛素受体、TLR-4和VEGF的水平。如黄体的存在和怀孕的实现所示,脂联素可恢复PCOS小鼠的排卵。这些发现表明脂联素可有效促进无排卵PCOS小鼠的生育能力。我们推测全身性脂联素治疗可能是管理PCOS的一种有前景的治疗策略。

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