College of Basic Medical Sciences, Hubei University of Chinese Medicine, Wuhan, China.
Hubei Shizhen Laboratory, Hubei University of Chinese Medicine, Wuhan, China.
Climacteric. 2024 Aug;27(4):421-432. doi: 10.1080/13697137.2024.2354742. Epub 2024 Jun 19.
The main purpose of this study was to elucidate the anti-apoptotic effects of curculigoside (CUR) on ovarian granulosa cells (GCs) in a mouse model of cyclophosphamide (CTX)-induced premature ovarian failure (POF).
Intraperitoneal injection of CTX (100 mg/kg body weight) induced POF in mice. Thirty-six female mice were divided into six groups: blank group; POF model group; low-dose CUR group; medium-dose CUR group; high-dose CUR group; and estradiol benzoate group. Mice were orally administered for 28 consecutive days. Twenty-four hours after the completion of treatment, mice were weighed and euthanized, and blood was collected from the eyeball under anesthesia. The ovaries were surgically separated and weighed, and the ovarian index was calculated. Hematoxylin-eosin (HE) staining was used to observe follicular development and corpus luteum morphology in the ovaries. Serum levels of follicle stimulating hormone (FSH), anti-Müllerian hormone (AMH) and estradiol (E2) were measured. Superoxide dismutase (SOD) activity, glutathione peroxidase (GSH-Px) content and malondialdehyde (MDA) levels in ovarian tissue were determined. The GC apoptosis level was measured. Western blotting was used to detect protein expression levels of Beclin-1, LC3, P62, AKT, p-AKT, mTOR and p-mTOR in the ovaries.
The results showed that CUR can improve body weight and ovarian index; promote follicular development and reduce follicular atresia; improve FSH, AMH and E2 levels; downregulate MDA levels and restore antioxidant enzyme activity; inhibit the autophagy level; activate the AKT/mTOR signaling pathway; and alleviate GC apoptosis.
CUR improves POF by activating the AKT/mTOR signaling pathway, inhibiting autophagy and alleviating GC apoptosis.
本研究旨在阐明毛蕊花糖苷（CUR）对环磷酰胺（CTX）诱导的小鼠卵巢早衰（POF）模型中卵巢颗粒细胞（GC）的抗凋亡作用。
腹腔注射 CTX（100mg/kg 体重）诱导小鼠 POF。将 36 只雌性小鼠分为 6 组：空白组；POF 模型组；低剂量 CUR 组；中剂量 CUR 组；高剂量 CUR 组；和苯甲酸雌二醇组。小鼠连续口服给药 28 天。治疗完成后 24 小时，小鼠称重并麻醉处死，从眼球采集血液。手术分离卵巢并称重，计算卵巢指数。苏木精-伊红（HE）染色观察卵巢卵泡发育和黄体形态。测定血清卵泡刺激素（FSH）、抗苗勒管激素（AMH）和雌二醇（E2）水平。测定卵巢组织中超氧化物歧化酶（SOD）活性、谷胱甘肽过氧化物酶（GSH-Px）含量和丙二醛（MDA）水平。测定 GC 凋亡水平。Western blot 检测卵巢中 Beclin-1、LC3、P62、AKT、p-AKT、mTOR 和 p-mTOR 蛋白表达水平。
结果表明，CUR 可以改善体重和卵巢指数；促进卵泡发育，减少卵泡闭锁；提高 FSH、AMH 和 E2 水平；下调 MDA 水平并恢复抗氧化酶活性；抑制自噬水平；激活 AKT/mTOR 信号通路；并减轻 GC 凋亡。
CUR 通过激活 AKT/mTOR 信号通路、抑制自噬和减轻 GC 凋亡来改善 POF。
