摘 要：为研究刺五加注射液（ASI）对多囊卵巢综合征（PCOS）大鼠卵巢功能的影响及相关机制，通过用来曲唑（1 mg/kg）连续灌胃21 d制备PCOS大鼠模型，将大鼠设为正常组、模型组、ASI组、激动剂组和抑制剂组，每组8只。治疗4周后，称量大鼠体质量；检测空腹血糖和空腹胰岛素水平，计算胰岛素抵抗指数（HOMA-IR）；用ELISA法检测血清中抗缪勒管激素（AMH）、睾酮（T）、雌二醇（E2）、促黄体生成素（LH）、促卵泡生成素（FSH）水平，并计算LH/FSH的比值；计算卵巢指数；用苏木精-伊红（HE）、原位末端标记（TUNEL）染色法检查卵巢组织病变和细胞凋亡状况；用分光光度法检测卵巢组织中丙二醛（MDA）的含量和超氧化物歧化酶（SOD）、过氧化氢酶（CAT）的活性；用RT-qPCR法检测Nrf2、HO-1 mRNA的表达水平，用Western blot法检测核因子E2相关因子2（Nrf2）、血红素氧合酶-1（HO-1）、B淋巴细胞瘤-2（Bcl-2）、Bcl-2相关X蛋白（Bax）、半胱氨酸蛋白酶3（Cas-3）、活化型Cas-3（C-Cas-3）蛋白的表达水平。结果显示：与模型组相比，ASI组和激动剂组大鼠的体质量、HOMA-IR以及空腹血糖、空腹胰岛素、AMH、T、LH水平和LH/FSH降低，E2、FSH水平升高；卵巢组织病变明显改善，卵巢指数、囊性卵泡数及卵巢细胞凋亡指数降低，黄体数升高；卵巢组织中MDA含量降低，SOD和CAT活性升高，Nrf2、HO-1 mRNA的表达水平及Nrf2、HO-1、Bcl-2蛋白的表达水平升高，Bax、C-Cas-3蛋白的表达水平及C-Cas-3/Cas-3降低，上述差异均有统计学意义（P<0.05）；与ASI组相比，激动剂组对PCOS大鼠各项检测指标的作用明显增强，抑制剂组对各项检测指标的作用明显减弱，差异均有统计学意义（P<0.05）。研究表明，ASI可能通过上调Nrf2/HO-1通路来改善PCOS大鼠的卵巢功能。该结果为PCOS的治疗提供了新的思路。
关键词：多囊卵巢综合征；刺五加注射液；卵巢功能；凋亡；Nrf2/HO-1通路
中图分类号：R285.5                              文献标志码：A                     DOI：10.3969/j.issn.1007-7146.2025.04.006

Abstract: To investigate the effects and related mechanism of acanthopanax senticosus injection (ASI) on ovarian function in rats with polycystic ovary syndrome (PCOS). The PCOS rat model was prepared by continuously gavage of letrozole (1 mg/kg) for 21 days, and the normal group, model group, ASI group, activator group and inhibitor group, with 8 rats in each group. After 4 weeks of treatment, the body mass was weighted, the level of fasting blood glucose and fasting insulin in serum were measured, and the homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. The level of anti-mullerian hormone (AMH), testosterone (T), estradiol (E2), luteinizing hormone (LH) and follicle stimulating hormone (FSH) in serum were measured by ELISA, and the LH/FSH was calculated. The ovarian index was calculated. The pathological changes and cell apoptosis ovarian tissue was examined by hematoxylin-eosin (HE) staining or TdT mediated dUDP nick end labeling (TUNEL) staining. The content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), catalase (CAT) in ovarian tissues were detected by spectrophotometer staining. The mRNA expression of Nrf2, HO-1 were detected by RT-qPCR; the protein expression of nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), B-lymphomatoma-2 (Bcl-2), Bcl-2 related X protein (Bax), Caspase-3 (Cas-3), Cleaved Caspase-3 (C-Cas-3) were detected by Western blot. The results showed that: compared with the model group, the body mass, HOMA-IR and the level of fasting blood glucose, fasting insulin, AMH, T, LH and LH/FSH decreased for the rats in the ASI group and activator group, and the level of E2, FSH increased. The pathological changes of ovarian tissue were improved, the ovarian index, cystic follicle number and apoptosis index of ovarian cell were decreased, and the corpus luteum number was increased. The content of MDA in ovarian tissue was decreased, the activity of SOD and CAT were increased. The mRNA expression level of Nrf2, HO-1 and the protein expression level of Nrf2, HO-1, Bcl-2 increased, the protein expression level of Bax, C-Cas-3 and the C-Cas-3/Cas-3 decreased. All of the differences were statistically significant (P<0.05). Compared with the ASI group, the activator group showed significantly enhanced effects on various detection indicators in PCOS rats, while the inhibitor group showed significantly weakened effects on various detection indicators, the differences were statistically significant (P<0.05). Studies have showed that ASI may improve ovarian function in PCOS rats by upregulating the Nrf2/HO-1 pathway, which providing a new approach for PCOS treatment.
Key words: polycystic ovary syndrome; acanthopanax senticosus injection; ovarian function; apoptosis; Nrf2/HO-1 pathway
（Acta Laser Biology Sinica, 2025, 34(4): 328-339）