目的通过sc丙酸睾酮诱导无排卵型月经不调大鼠模型，考察乌鸡白凤软胶囊（WJBFSC）调经作用。方法取同批出生9日龄雌性大鼠，随机取10只颈背部sc无菌色拉油作为对照组，其余大鼠颈背部sc丙酸睾酮每只1.25 mg，常规饲养。22日龄断奶，待73日龄阴道开口，连续阴道上皮细胞涂片2个性周期，选取阴道上皮无周期性变化大鼠作为无排卵月经不调大鼠模型。将筛选出的模型大鼠按体质量分为6组：模型组、氯米芬（阳性对照，5.2 mg·kg^-1，临床等效剂量）组、定坤丹组（1.4 g·kg^-1，临床等效剂量）和WJBFSC低、中、高剂量组（0.3、0.6、1.2 g·kg^-1，0.6 g·kg^-1为临床等效剂量），每组10只。83 d龄时各给药组开始按剂量ig给药，每天1次，连续给药6周，对照组和模型组给予等体积的0.1% CMCNa。每周检测体温、体质量变化，停药前10 d阴道涂片观察性周期，计算子宫及卵巢指数，ELISA法检测血清孕酮（Pg）、促卵泡激素（FSH）、雌二醇（E₂）、促黄体生成素（LH）、催乳素（PRL）、睾酮（T）、促性腺激素释放激素（GnRH）含量，子宫、卵巢、阴道组织苏木素-伊红（HE）染色后病理检测。结果对照组大鼠阴道上皮细胞涂片呈周期性变化，周期在4～5 d，发情周期变化规律；模型组大鼠发情周期明显紊乱，表现为发情周期顺序紊乱或后期及间期持续时间延长。与模型组比较，WJBFSC对模型大鼠的性周期紊乱有一定的改善作用；低、高剂量组大鼠体质量均显著降低（P＜0.01、0.001），中剂量组有降低趋势；低、中、高剂量组大鼠体温均显著升高（P＜0.01、0.001）；高剂量组子宫指数和卵巢指数显著升高（P＜0.05）；低剂量组FSH、PRL含量显著降低（P＜0.05、0.01），E₂、Pg含量显著升高（P＜0.05、0.01），中剂量组LH、PRL含量显著降低（P＜0.05、0.01），Pg含量显著升高（P＜0.001），高剂量组LH、PRL、T含量显著降低（P＜0.05、0.001），Pg含量显著升高（P＜0.01）；各给药组卵巢各级卵泡数目增多（P＜0.05、0.001），部分可见较成熟卵泡和黄体；子宫腺体功能较活跃，间质较疏松，可见较多白细胞浸润；宫颈及阴道角质层部分增厚，并可见细胞脱落，生理周期功能较模型组有所改善。结论 WJBFSC可以改善无排卵型月经不调大鼠体质量、体温异常变化，升高卵巢、子宫指数，有效改善血清性激素水平及子宫、卵巢、阴道组织病变，对该模型有较好的药效作用。

Abstract Objective To investigate the regulatory effect of Wuji Baifeng Soft Capsule (WJBFSC) on anovulatory menstrual irregularity in a rat model induced by subcutaneous injection of testosterone propionate. Methods Female rats of the same batch at 9 days of age were randomly divided into two groups: 10 rats received subcutaneous injection of sterile salad oil at the nape as the control group, while the remaining rats received subcutaneous injection of testosterone propionate (1.25 mg) at the nape and were maintained under conventional feeding conditions. After weaning at 22 days of age, vaginal opening was observed at 73 days of age. Rats exhibiting acyclic vaginal epithelial changes over two consecutive estrous cycles were selected as the anovulatory menstrual irregularity model. The screened model rats were stratified by body weight into six groups (n = 10): The selected model rats were divided into six groups based on body weight: model group, clomiphene citrate (positive control, 5.2 mg·kg^-1, clinically equivalent dose) group, Dingkun Dan group (1.4 g·kg^-1, clinically equivalent dose), and WJBFSC low, medium, and high dose groups (0.3, 0.6, 1.2 g·kg^-1, with 0.6 g·kg^-1 being the clinically equivalent dose), with 10 rats in each group. At the age of 83 days, each treatment group began to receive ig administration according to the dose, once daily, for six consecutive weeks. The control group and model group were given equal volumes of 0.1% CMC-Na. Uterine and ovarian coefficients were calculated. Serum sex hormone levels, including progesterone (Pg) and follicle-stimulating hormone (FSH), were determined by ELISA. Histopathological examination of uterine, ovarian, and vaginal tissues was performed using HE staining. Results Rats in the control group exhibited regular cyclical changes in vaginal epithelial cells with estrous cycles of 4-5 days, demonstrating normal estrous periodicity. In contrast, model group rats showed markedly disrupted estrous cycles, characterized by disordered cycle sequence or prolonged diestrus and estrus phases. Compared with the model group, WJBFSC demonstrated a certain ameliorative effect on estrous cycle disturbances in model rats. Both low- and high-dose groups exhibited significant reductions in body weight (P < 0.01, 0.001), with a decreasing trend observed in the medium-dose group. Significant elevations in body temperature were observed in the low-, medium-, and high-dose groups (P < 0.01, 0.001). The high-dose group showed significant increases in both uterine and ovarian coefficients (P < 0.05). In the low-dose group, FSH and prolactin (PRL) levels were significantly decreased (P < 0.05, 0.01), while estradiol (E₂) and Pg levels were significantly elevated (P < 0.05, 0.01). The medium-dose group exhibited significant reductions in luteinizing hormone (LH) and PRL levels (P < 0.05, 0.01) and a significant increase in Pg level (P < 0.001). The high-dose group demonstrated significant decreases in LH, PRL, and testosterone (T) levels (P < 0.05, 0.001) and a significant increase in Pg level (P < 0.01). In all treatment groups, the number of ovarian follicles at various developmental stages increased, with some mature follicles and corpora lutea observable. Uterine glands appeared functionally active with relatively loose stroma and increased leukocyte infiltration. Partial thickening of the keratinized layer in the cervix and vagina was observed, with visible cell desquamation. Physiological cyclical function improved compared with the model group. Conclusion WJBFSC can ameliorate abnormal body weight and temperature changes, increase ovarian and uterine coefficients, effectively improve serum sex hormone profiles, and attenuate histopathological lesions in uterine, ovarian, and vaginal tissues in the anovulatory menstrual irregularity rat model, demonstrating significant pharmacological efficacy in this model.

R965

国家科技重大专项——“四大慢病重大专项”（2025ZD0549700）