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姜黄素联合有氧运动通过抑制多囊卵巢综合征样大鼠高胰岛素诱导的内质网应激通路改善卵泡功能障碍。

Curcumin in Combination with Aerobic Exercise Improves Follicular Dysfunction via Inhibition of the Hyperandrogen-Induced IRE1/XBP1 Endoplasmic Reticulum Stress Pathway in PCOS-Like Rats.

机构信息

State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing 210093, China.

Danyang Hospital Affiliated to Nantong University, Danyang, Jiangsu 212300, China.

出版信息

Oxid Med Cell Longev. 2021 Dec 26;2021:7382900. doi: 10.1155/2021/7382900. eCollection 2021.

DOI:10.1155/2021/7382900
PMID:34987702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8720591/
Abstract

Combining diet with exercise can improve health and performance. Exercise can reduce androgen excess and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients. Curcumin is also presumed to improve the follicle development disorder. Here, we investigated the effects of a combination therapy of oral intake of curcumin and exercise on hyperandrogen-induced endoplasmic reticulum (ER) stress and ovarian granulosa cell (GC) apoptosis in rats with PCOS. We generated a PCOS model via continuous dehydroepiandrosterone subcutaneous injection into the necks of Sprague Dawley rats for 35 days. PCOS-like rats then received curcumin treatment combined with aerobic (treadmill) exercise for 8 weeks. We found that compared to control rats, the ovarian tissue and ovarian GCs of hyperandrogen-induced PCOS rats showed increased levels of ER stress-related genes and proteins. Hyperandrogen-induced ovarian GC apoptosis, which was mediated by excessive ER stress and unfolded protein response (UPR) activation, could cause follicle development disorders. Both curcumin gavage and aerobic exercise improved ovarian function via inhibiting the hyperandrogen-activated ER stress IRE1-XBP1 pathway. Dihydrotestosterone- (DHT-) induced ER stress was mitigated by curcumin/irisin or 48C (an ER stress inhibitor) in primary GC culture. In this in vitro model, the strongly expressed follicular development-related genes , , and were also downregulated.

摘要

饮食与运动相结合可以改善健康和性能。运动可以减少多囊卵巢综合征(PCOS)患者的雄激素过多和胰岛素抵抗(IR)。姜黄素也被认为可以改善卵泡发育障碍。在这里,我们研究了口服姜黄素和运动联合治疗对多囊卵巢综合征大鼠高雄激素诱导的内质网(ER)应激和卵巢颗粒细胞(GC)凋亡的影响。我们通过连续将脱氢表雄酮皮下注射到 Sprague Dawley 大鼠颈部 35 天来生成 PCOS 模型。然后,PCOS 样大鼠接受姜黄素治疗并结合有氧运动(跑步机)锻炼 8 周。我们发现,与对照组大鼠相比,高雄激素诱导的 PCOS 大鼠的卵巢组织和卵巢 GC 显示出更多的 ER 应激相关基因和蛋白。高雄激素诱导的卵巢 GC 凋亡是由过度的 ER 应激和未折叠蛋白反应(UPR)激活介导的,会导致卵泡发育障碍。姜黄素灌胃和有氧运动均可通过抑制高雄激素激活的 ER 应激 IRE1-XBP1 通路来改善卵巢功能。姜黄素/鸢尾素或 48C(一种 ER 应激抑制剂)可减轻二氢睾酮(DHT)诱导的 ER 应激在原代 GC 培养物中。在这个体外模型中,强烈表达的卵泡发育相关基因 、 、 和 也被下调。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/53f8a88fe952/OMCL2021-7382900.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/d9e505e53e18/OMCL2021-7382900.001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/53f8a88fe952/OMCL2021-7382900.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/d9e505e53e18/OMCL2021-7382900.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/143598e8bc2a/OMCL2021-7382900.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/5e540bf3a0b2/OMCL2021-7382900.003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f0b7/8720591/53f8a88fe952/OMCL2021-7382900.006.jpg

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