Xu Hui-Xian, Lin Shu-Xia, Gong Yuewen, Huo Zi-Xuan, Zhao Cheng-Yun, Zhu Hong-Mei, Xi Sheng-Yan
Cancer Research Center, School of Medicine, Xiamen University, Xiamen, China.
Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China.
Front Pharmacol. 2020 Mar 24;11:245. doi: 10.3389/fphar.2020.00245. eCollection 2020.
Chronic stress has been known to impair the female reproductive function, but the mechanism remains to be further investigated. Chaiyu-Dixian Formula (CYDXF) has been reported to regulate human endocrine disorders clinically. However, whether this formula can affect chronic stress-induced ovarian follicular development is not clear.
To examine effects of CYDXF on follicular development and explore possible mech anisms in a chronic unpredictable mild stress (CUMS) model.
Adult female rats were randomly divided into 5 groups control group, CUMS group (saline treatment), CUMS+Estradiol (E) (0.1 mg/kg) group, CUMS+CYDXF (2.73 g/kg) group, and CUMS+CYDXF (5.46 g/kg) group. Body weights and behavioral tests were documented. Serum hormone levels were determined by enzyme-linked immunosorbent assay (ELISA). Western blotting was used to detect the protein levels in the PI3K/Akt pathway and brain-derived neurotrophic factor (BDNF). The follicles were analyzed and classified according to their morphological characterization.
CYDXF relieved depression-like behaviors and ameliorated the abnormality in rat estrous cycle within the rat model of CUMS. Moreover, CYDXF could regulate endocrine disorders, increase the proportion of antral follicles as well as decrease the proportion of follicular atresia, which suggested that CYDXF could alleviate abnormal follicular development and improve overall ovarian function. Furthermore, CYDXF also activated the BDNF-mediated PI3K/Akt signaling pathway.
CYDXF (at dose of both 2.73 and 5.46 g/kg) attenuated chronic stress-induced abnormal ovarian follicular development by relieving depression-like behaviors and improving ovarian function through partly the regulation of the BDNF-mediated PI3K/Akt pathway.
已知慢性应激会损害女性生殖功能，但其机制仍有待进一步研究。柴胡-地仙方（CYDXF）在临床上已被报道可调节人类内分泌紊乱。然而，该方剂是否能影响慢性应激诱导的卵巢卵泡发育尚不清楚。
在慢性不可预测轻度应激（CUMS）模型中，研究CYDXF对卵泡发育的影响并探索其可能机制。
成年雌性大鼠随机分为5组：对照组、CUMS组（生理盐水处理）、CUMS + 雌二醇（E）（0.1 mg/kg）组、CUMS + CYDXF（2.73 g/kg）组和CUMS + CYDXF（5.46 g/kg）组。记录体重和行为测试结果。采用酶联免疫吸附测定（ELISA）法测定血清激素水平。用蛋白质印迹法检测PI3K/Akt信号通路和脑源性神经营养因子（BDNF）的蛋白水平。根据卵泡的形态特征进行分析和分类。
在CUMS大鼠模型中，CYDXF缓解了抑郁样行为，并改善了大鼠发情周期的异常。此外，CYDXF可调节内分泌紊乱，增加窦卵泡比例并降低卵泡闭锁比例，这表明CYDXF可减轻卵泡发育异常并改善整体卵巢功能。此外，CYDXF还激活了BDNF介导的PI3K/Akt信号通路。
CYDXF（2.73 g/kg和5.46 g/kg剂量）通过缓解抑郁样行为和部分通过调节BDNF介导的PI3K/Akt信号通路改善卵巢功能，减轻慢性应激诱导的异常卵巢卵泡发育。
