Fujian Provincial Key Laboratory of Reproductive Health Research, Department of Obstetrics and Gynecology, School of Medicine, The First Affiliated Hospital of Xiamen University, Xiamen University, 361102, Xiamen, Fujian, China.
Department of Obstetrics and Gynecology, Key Laboratory for Major Obstetric Diseases of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
J Ovarian Res. 2023 Aug 26;16(1):176. doi: 10.1186/s13048-023-01215-0.
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.
中医药在治疗各种妇科疾病方面已有很长的历史。在各种中药中，定坤丹（DK）已被用于治疗女性妇科疾病。然而，DK 对多囊卵巢综合征（PCOS）的治疗效果及其潜在作用的靶组织仍需探索。本研究旨在从代谢、内分泌和生育三个方面探讨 DK 对 PCOS 小鼠的治疗作用，并确定棕色脂肪组织是否为缓解 PCOS 表型的靶器官。
通过皮下注射 DHEA 构建 PCOS 小鼠模型。检查小鼠的动情周期、排卵和妊娠结局。通过 ELISA 测定血清中激素包括 LH、FSH、雌激素和睾酮的水平。对不同处理的小鼠进行葡萄糖敏感性和胰岛素敏感性测定。分析棕色脂肪组织的组织形态和脂质含量。对棕色脂肪组织进行 RNA-Seq 分析，并通过实时 PCR 确认关键代谢标志物基因的不同表达。
数据表明，DK 治疗的 PCOS 小鼠的生育能力显著提高，代谢紊乱得到部分恢复。DHEA 诱导的棕色脂肪组织变白和 UCP1 表达减少均被 DK 挽救。RNA-Seq 数据进一步表明，DK 至少部分挽救了 DHEA 诱导的脂肪分解基因和氧化磷酸化基因的下调。
DK 对 DHEA 处理的 PCOS 小鼠具有治疗作用，棕色脂肪组织至少是缓解 PCOS 的一个关键靶器官。这不仅通过调节棕色脂肪的脂质动员来实现，而且还通过恢复其产热功能来实现。
