Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation.

Dingkun pill alleviates metabolic abnormalities in polycystic ovary syndrome through brown adipose tissue activation.
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DOI:
10.1186/s13048-023-01215-0
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发表时间:
2023-08-26
影响因子:
4
通讯作者:
Kong, Shuangbo
Kong, Shuangbo
中科院分区:
医学3区
文献类型:
--
作者:
Gu, Mengqing;Cai, Han;Deng, Weinan;Tang, Yedong;Du, Shuailin;Wang, Peiran;Deng, Wenbo;Wang, Haibin;Sun, Aijun;Kong, Shuangbo

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长期以来,中医药一直被用于治疗各种妇科疾病。在众多的中药中,定坤丸一直被用于治疗女性妇科疾病。但DK对PCOS的治疗效果及其对靶组织的潜在作用还需进一步探讨。本研究旨在从代谢、内分泌和生育三个方面探讨DK对小鼠PCOS的治疗作用,并确定棕色脂肪组织是否为缓解PCOS表型的靶器官。皮下注射DHEA建立PCOS小鼠模型。在小鼠中检查发情周期、排卵和妊娠结果。ELISA法测定血清LH、FSH、雌激素和睾酮水平。测定不同处理小鼠的葡萄糖敏感性和胰岛素敏感性。对棕色脂肪组织进行组织形态学和脂质含量分析。对棕色脂肪组织进行RNA-Seq,并通过实时PCR证实关键代谢标志物基因的不同表达。数据显示,DK治疗的PCOS小鼠的生育能力显著提高,代谢紊乱部分恢复。DK可挽救DHEA诱导的棕色脂肪组织增生和UCP 1表达减少。RNA-Seq数据进一步证明DHEA诱导的脂解基因和氧化磷酸化基因的下调至少部分地被棕色脂肪组织中的DK拯救。DK对DHEA处理的小鼠PCOS具有治疗作用,棕色脂肪组织是减轻PCOS的至少一个关键靶器官。这不仅是通过调节棕色脂肪的脂质动员,而且还恢复其产热功能来实现的。在线版本包含补充材料,可通过10.1186/s13048-023-01215-0获得。
Traditional Chinese medicine has been used for a long time to treat a variety of gynecological diseases. Among various traditional Chinese medicine, Dingkun Pill (DK) has been used for the treatment of female gynecological diseases. However, DK therapeutic effect on PCOS and the target tissue for its potential effect need to be explored. This study aims to explore the therapeutic effect of DK for PCOS in mice from three aspects: metabolism, endocrine and fertility, and determine whether the brown adipose tissue is the target organ to alleviate the PCOS phenotype. PCOS mouse model was constructed by subcutaneous injection of DHEA. The estrous cycle, ovulation, and pregnancy outcome was examined in mice. The level of hormone including the LH, FSH, estrogen and testosterone in the serum were measured by ELISA. Both the glucose sensitivity and insulin sensitivity were determined in mice with different treatment. The histomorphology and lipid contents in the brown adipose tissue were analyzed. RNA-Seq was conducted for the brown adipose tissue and different expression of critical metabolism marker genes was confirmed by real-time PCR. The data showed that the fertility in PCOS mice with DK treatment was significantly increased, and the metabolic disorder was partially restored. Both the whiten of brown adipose tissue and reduced UCP1 expression induced by DHEA was rescued by the DK. The RNA-Seq data further demonstrated both the DHEA induced downregulation of lipolysis genes and oxidative phosphorylation genes were at least partially rescued by DK in the brown adipose tissue. DK has therapeutic effect on PCOS in DHEA treated mice and the brown adipose tissue is at least one critical target organ to alleviate the PCOS. This is achieved by not only regulating the lipid mobilization of brown adipose, but also restoring its thermogenic function. The online version contains supplementary material available at 10.1186/s13048-023-01215-0.
DOI: 10.1056/nejmcp1514916
发表时间: 2016-07-07
期刊: The New England journal of medicine
影响因子: --
作者:
McCartney CR;Marshall JC
通讯作者: Marshall JC
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发表时间: 2004-06-01
影响因子: 5.8
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发表时间: 2019-10-01
影响因子: 3.6
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DOI: 10.1210/jc.2017-01958
发表时间: 2018-02-01
影响因子: 5.8
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