Resveratrol improves follicular development of PCOS rats via regulating glycolysis pathway and targeting SIRT1
Resveratrol improves follicular development of PCOS rats via regulating glycolysis pathway and targeting SIRT1
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白藜芦醇通过调节糖酵解途径并靶向SIRT1改善PCOS大鼠的卵泡发育
DOI：
10.1080/19396368.2022.2125855
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发表时间：
2022-10-20
影响因子：
2.4
通讯作者：
Zhang，Shun
中科院分区：
文献类型：
--
作者：
Huo，Peng;Li，Man;Zhang，Shun
摘要多囊卵巢综合征(PCOS)是一种以代谢紊乱为特征的疾病。本研究旨在观察白藜芦醇对多囊卵巢综合征大鼠排卵的影响。用实时定量聚合酶链式反应和免疫组织化学方法检测基因和蛋白的表达水平。TNUEL法检测卵巢细胞凋亡率。采用高效液相色谱-串联质谱仪对代谢产物进行了鉴定。白藜芦醇可减轻PCOS大鼠动情周期紊乱，改善颗粒细胞层，逆转PCOS大鼠卵巢组织颗粒细胞增殖减少、细胞凋亡增加的现象。白藜芦醇可恢复PCOS卵巢糖酵解限速基因mRNA表达水平的变化。PCOS大鼠卵巢组织中乳酸脱氢酶A(LDH-A)、丙酮酸激酶同工酶M2(PKM2)和sirtuin 1(SIRT1)的表达显著下调，而白藜芦醇治疗组大鼠卵巢组织LDH-A、PKM2和SIRT1的表达显著上调。总之，白藜芦醇对PCOS大鼠的保护作用可能与调节糖酵解相关的介质包括PKM2、LDH-A和SIRT1有关。白藜芦醇可能是缓解多囊卵巢综合征发展的一个很好的候选药物。
Abstract Polycystic ovary syndrome (PCOS) is a disease characterized by metabolic disorders. This study aimed to examine the effects of resveratrol treatment on ovulation in the PCOS rat model. Quantitative real-time PCR and immunohistochemistry were used to determine the mRNA and protein expression levels. TNUEL assay was used to evaluate cell apoptosis in ovary. The metabolites were evaluated by liquid chromatography with tandem mass spectrometry. Resveratrol alleviated disrupted estrous cycle and improved granular cell layers, and reversed the decreased proliferation and increased cell apoptosis of granulosa cells in the ovarian tissues of PCOS rats. Resveratrol restored the changes in the mRNA expression levels in the rate-limiting genes of glycolysis in the PCOS ovary. The expression of lactate dehydrogenase A (LDH-A), pyruvate kinase isozyme M2 (PKM2), and sirtuin 1 (SIRT1) was significantly downregulated in ovarian tissues of the PCOS rats; while the resveratrol treatment significantly increased the expression of LDH-A, PKM2, and SIRT1 in the ovarian tissues of PCOS rats. Collectively, the protective effects of resveratrol in the PCOS rats may be associated with the regulation of glycolysis-related mediators including PKM2, LDH-A, and SIRT1. Resveratrol may represent a good candidate in alleviating the development of PCOS.